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n2:pmcid
PMC0
bibo:doi
10.1083%2Fjcb.200909003
n5:contains
_:vb6524655 _:vb6524822 _:vb6524828 _:vb6524751 _:vb6524704 _:vb6524718
Subject Item
_:vb6524655
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n5:Section
dc:title
the modes of cell migration
n5:contains
_:vb6524696 _:vb6524697 _:vb6524698 _:vb6524699 _:vb6524700 _:vb6524701 _:vb6524702 _:vb6524703 _:vb6524688 _:vb6524689 _:vb6524690 _:vb6524691 _:vb6524692 _:vb6524693 _:vb6524694 _:vb6524695 _:vb6524680 _:vb6524681 _:vb6524682 _:vb6524683 _:vb6524684 _:vb6524685 _:vb6524686 _:vb6524687 _:vb6524672 _:vb6524673 _:vb6524674 _:vb6524675 _:vb6524676 _:vb6524677 _:vb6524678 _:vb6524679 _:vb6524664 _:vb6524665 _:vb6524666 _:vb6524667 _:vb6524668 _:vb6524669 _:vb6524670 _:vb6524671 _:vb6524656 _:vb6524657 _:vb6524658 _:vb6524659 _:vb6524660 _:vb6524661 _:vb6524662 _:vb6524663
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was then extended to include molecular parameters, such as cytoskeletal organization, the type of cell–matrix interaction and force generation, and the modification of the tissue structure imposed by migrating cells (Friedl et al., 1998b; Thiery, 2002; Friedl, 2004; Lämmermann and Sixt, 2009; Sanz-Moreno and Marshall, 2009).
n2:mentions
n3:9858334
Subject Item
_:vb6524657
rdf:type
n2:Context
rdf:value
to include molecular parameters, such as cytoskeletal organization, the type of cell–matrix interaction and force generation, and the modification of the tissue structure imposed by migrating cells (Friedl et al., 1998b; Thiery, >>2002<<; Friedl, 2004; Lämmermann and Sixt, 2009; Sanz-Moreno and Marshall, 2009). As main categories, cell move either individually (amoeboid or mesenchymal) or collectively (the migration of cohesive multicellular units; Fig.
n2:mentions
n3:12189386
Subject Item
_:vb6524658
rdf:type
n2:Context
rdf:value
molecular parameters, such as cytoskeletal organization, the type of cell–matrix interaction and force generation, and the modification of the tissue structure imposed by migrating cells (Friedl et al., 1998b; Thiery, 2002; Friedl, >>2004<<; Lämmermann and Sixt, 2009; Sanz-Moreno and Marshall, 2009). As main categories, cell move either individually (amoeboid or mesenchymal) or collectively (the migration of cohesive multicellular units; Fig.
n2:mentions
n3:15037300
Subject Item
_:vb6524659
rdf:type
n2:Context
rdf:value
as cytoskeletal organization, the type of cell–matrix interaction and force generation, and the modification of the tissue structure imposed by migrating cells (Friedl et al., 1998b; Thiery, 2002; Friedl, 2004; Lämmermann and Sixt, >>2009<<; Sanz-Moreno and Marshall, 2009). As main categories, cell move either individually (amoeboid or mesenchymal) or collectively (the migration of cohesive multicellular units; Fig.
n2:mentions
n3:19523798
Subject Item
_:vb6524660
rdf:type
n2:Context
rdf:value
the type of cell–matrix interaction and force generation, and the modification of the tissue structure imposed by migrating cells (Friedl et al., 1998b; Thiery, 2002; Friedl, 2004; Lämmermann and Sixt, 2009; Sanz-Moreno and Marshall, >>2009<<). As main categories, cell move either individually (amoeboid or mesenchymal) or collectively (the migration of cohesive multicellular units; Fig.
n2:mentions
n3:19372747
Subject Item
_:vb6524661
rdf:type
n2:Context
rdf:value
As main categories, cell move either individually (amoeboid or mesenchymal) or collectively (the migration of cohesive multicellular units; Fig. 1 and Table I; Friedl, >>2004<<). Although these terms are arguably arbitrary and the molecular discrimination between the certain modes is incomplete, they help to simplify and categorize an otherwise diffuse literature and allow dissection of the molecular machineries
n2:mentions
n3:15037300
Subject Item
_:vb6524662
rdf:type
n2:Context
rdf:value
some stem cellsPoorly adhesive; soft embryonic connective tissue; obligate 3DAsymmetric bleb-rich cortical actomyosin cytoskeleton, low polarity; low migration speed (below 1 µm/min)Blebby-to-pseudopodal transitionsBlaser et al., >>2006<<; Yoshida and Soldati, 2006    Amoeboid, pseudopodalLeukocytes, including dendritic cells; Dictyostelium discoideumLoose primordial or mature connective tissue; 2D or 3DPoorly adhesive, no formation of focal adhesions; Rac-driven anterior
n2:mentions
n3:17084355
Subject Item
_:vb6524663
rdf:type
n2:Context
rdf:value
adhesive; soft embryonic connective tissue; obligate 3DAsymmetric bleb-rich cortical actomyosin cytoskeleton, low polarity; low migration speed (below 1 µm/min)Blebby-to-pseudopodal transitionsBlaser et al., 2006; Yoshida and Soldati, >>2006<<    Amoeboid, pseudopodalLeukocytes, including dendritic cells; Dictyostelium discoideumLoose primordial or mature connective tissue; 2D or 3DPoorly adhesive, no formation of focal adhesions; Rac-driven anterior protrusion with
n2:mentions
n3:16926192
Subject Item
_:vb6524664
rdf:type
n2:Context
rdf:value
2D or 3DPoorly adhesive, no formation of focal adhesions; Rac-driven anterior protrusion with counterbalance by Rho/ROCK in other cell parts; relatively rapid migration (10 µm/min)Amoeboid-to-mesenchymal transitionYoshida and Soldati, >>2006<<; Lämmermann et al., 2008    MesenchymalFibroblasts, neural crest cells, sarcoma cells, dedifferentiated cancer cells of different originLoose or dense primordial or mature connective tissue; usually associated with fibrin or collagen
n2:mentions
n3:16926192
Subject Item
_:vb6524665
rdf:type
n2:Context
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no formation of focal adhesions; Rac-driven anterior protrusion with counterbalance by Rho/ROCK in other cell parts; relatively rapid migration (10 µm/min)Amoeboid-to-mesenchymal transitionYoshida and Soldati, 2006; Lämmermann et al., >>2008<<    MesenchymalFibroblasts, neural crest cells, sarcoma cells, dedifferentiated cancer cells of different originLoose or dense primordial or mature connective tissue; usually associated with fibrin or collagen remodelingModerately to
n2:mentions
n3:18451854
Subject Item
_:vb6524666
rdf:type
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with ECM; high contractility; high anterior Rac activity counterbalanced by Rho in other cell parts; slow migration (0.1–1 µm/min)Mesenchymal-to-amoeboid transition; mesenchymal-to-epithelial/collective transitionWolf et al., 2003a, 2007; Grinnell, 2008; Paňková et al., 2009; Thiery, 2002Multicellular    Chain migration, cell streamingNeural crest cells, fibroblastsJoint ECM tracks?
n2:mentions
n3:12527751
Subject Item
_:vb6524667
rdf:type
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with ECM; high contractility; high anterior Rac activity counterbalanced by Rho in other cell parts; slow migration (0.1–1 µm/min)Mesenchymal-to-amoeboid transition; mesenchymal-to-epithelial/collective transitionWolf et al., 2003a, >>2007<<; Grinnell, 2008; Paňková et al., 2009; Thiery, 2002Multicellular    Chain migration, cell streamingNeural crest cells, fibroblastsJoint ECM tracks?
n2:mentions
n3:17618273
Subject Item
_:vb6524668
rdf:type
n2:Context
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contractility; high anterior Rac activity counterbalanced by Rho in other cell parts; slow migration (0.1–1 µm/min)Mesenchymal-to-amoeboid transition; mesenchymal-to-epithelial/collective transitionWolf et al., 2003a, 2007; Grinnell, >>2008<<; Paňková et al., 2009; Thiery, 2002Multicellular    Chain migration, cell streamingNeural crest cells, fibroblastsJoint ECM tracks?
n2:mentions
n3:19083673
Subject Item
_:vb6524669
rdf:type
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counterbalanced by Rho in other cell parts; slow migration (0.1–1 µm/min)Mesenchymal-to-amoeboid transition; mesenchymal-to-epithelial/collective transitionWolf et al., 2003a, 2007; Grinnell, 2008; Paňková et al., 2009; Thiery, >>2002<<Multicellular    Chain migration, cell streamingNeural crest cells, fibroblastsJoint ECM tracks?
n2:mentions
n3:12189386
Subject Item
_:vb6524670
rdf:type
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Individual cells with temporary tiplike cell-cell contactsMigration arrest and integration into terminal tissueDavis and Trinkaus, >>1981<<; Kulesa and Fraser, 2000    CollectiveDictyostelium at slug stage, lateral line (zebrafish), border cells (Drosophila egg chamber), sprouting vessels, many epithelial and other cancer typesAny 2D and 3D ECM environment, resulting in
n2:mentions
n3:7310293
Subject Item
_:vb6524671
rdf:type
n2:Context
rdf:value
Individual cells with temporary tiplike cell-cell contactsMigration arrest and integration into terminal tissueDavis and Trinkaus, 1981; Kulesa and Fraser, >>2000<<    CollectiveDictyostelium at slug stage, lateral line (zebrafish), border cells (Drosophila egg chamber), sprouting vessels, many epithelial and other cancer typesAny 2D and 3D ECM environment, resulting in cohesive sheets or 3D strands,
n2:mentions
n3:10683170
Subject Item
_:vb6524672
rdf:type
n2:Context
rdf:value
coordination of multicellular leading edge protrusion and rear retraction; cell–cell communication during migrationCollective-to-single cell transitions (epithelial/collective-to-mesenchymal; collective-to-amoeboid)Hegerfeldt et al., >>2002<<; Thiery, 2002; Alexander et al., 2008; Friedl and Gilmour, 2009    Keratocyte-likeKeratinocytesObligate 2D surface or tissuePersistent gliding-type migration of spread-out cells with broad continuous leading lamella cadherin-based
n2:mentions
n3:11929834
Subject Item
_:vb6524673
rdf:type
n2:Context
rdf:value
of multicellular leading edge protrusion and rear retraction; cell–cell communication during migrationCollective-to-single cell transitions (epithelial/collective-to-mesenchymal; collective-to-amoeboid)Hegerfeldt et al., 2002; Thiery, >>2002<<; Alexander et al., 2008; Friedl and Gilmour, 2009    Keratocyte-likeKeratinocytesObligate 2D surface or tissuePersistent gliding-type migration of spread-out cells with broad continuous leading lamella cadherin-based cell–cell
n2:mentions
n3:12189386
Subject Item
_:vb6524674
rdf:type
n2:Context
rdf:value
edge protrusion and rear retraction; cell–cell communication during migrationCollective-to-single cell transitions (epithelial/collective-to-mesenchymal; collective-to-amoeboid)Hegerfeldt et al., 2002; Thiery, 2002; Alexander et al., >>2008<<; Friedl and Gilmour, 2009    Keratocyte-likeKeratinocytesObligate 2D surface or tissuePersistent gliding-type migration of spread-out cells with broad continuous leading lamella cadherin-based cell–cell junctionsNot knownKeren et al.,
n2:mentions
n3:18987875
Subject Item
_:vb6524675
rdf:type
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retraction; cell–cell communication during migrationCollective-to-single cell transitions (epithelial/collective-to-mesenchymal; collective-to-amoeboid)Hegerfeldt et al., 2002; Thiery, 2002; Alexander et al., 2008; Friedl and Gilmour, >>2009<<    Keratocyte-likeKeratinocytesObligate 2D surface or tissuePersistent gliding-type migration of spread-out cells with broad continuous leading lamella cadherin-based cell–cell junctionsNot knownKeren et al.,
n2:mentions
n3:19546857
Subject Item
_:vb6524676
rdf:type
n2:Context
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Friedl and Gilmour, 2009    Keratocyte-likeKeratinocytesObligate 2D surface or tissuePersistent gliding-type migration of spread-out cells with broad continuous leading lamella cadherin-based cell–cell junctionsNot knownKeren et al., >>2008<<
n2:mentions
n3:18497816
Subject Item
_:vb6524677
rdf:type
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Amoeboid migration commonly refers to the movement of rounded or ellipsoid cells that lack mature focal adhesions and stress fibers (Friedl et al., >>2001<<; Lämmermann and Sixt, 2009). There are two subtypes of amoeboid movement.
n2:mentions
n3:11590185
Subject Item
_:vb6524678
rdf:type
n2:Context
rdf:value
Amoeboid migration commonly refers to the movement of rounded or ellipsoid cells that lack mature focal adhesions and stress fibers (Friedl et al., 2001; Lämmermann and Sixt, >>2009<<). There are two subtypes of amoeboid movement.
n2:mentions
n3:19523798
Subject Item
_:vb6524679
rdf:type
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The first is the rounded, blebby migration of cells that do not adhere or pull on substrate but rather use a propulsive, pushing migration mode (Fackler and Grosse, >>2008<<; Sanz-Moreno and Marshall, 2009).
n2:mentions
n3:18541702
Subject Item
_:vb6524680
rdf:type
n2:Context
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The first is the rounded, blebby migration of cells that do not adhere or pull on substrate but rather use a propulsive, pushing migration mode (Fackler and Grosse, 2008; Sanz-Moreno and Marshall, >>2009<<). The second occurs in slightly more elongated amoeboid cells that generate actin-rich filopodia at the leading edge that engage in poorly defined, weak adhesive interaction with the substrate (Fig. 1; Yoshida and Soldati, 2006; Smith et
n2:mentions
n3:19372747
Subject Item
_:vb6524681
rdf:type
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The second occurs in slightly more elongated amoeboid cells that generate actin-rich filopodia at the leading edge that engage in poorly defined, weak adhesive interaction with the substrate (Fig. 1; Yoshida and Soldati, >>2006<<; Smith et al., 2007).
n2:mentions
n3:16926192
Subject Item
_:vb6524682
rdf:type
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1; Yoshida and Soldati, 2006; Smith et al., >>2007<<). In a special case of amoeboid movement, terminally matured nonadhesive dendritic cells produce dynamic actin-rich dendrites, instead of blebs, at their leading edge that cause these cell to become entangled with the ECM substrate during
n2:mentions
n3:17218464
Subject Item
_:vb6524683
rdf:type
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movement, terminally matured nonadhesive dendritic cells produce dynamic actin-rich dendrites, instead of blebs, at their leading edge that cause these cell to become entangled with the ECM substrate during migration (Gunzer et al., >>1997<<; Lämmermann et al., 2008).
n2:mentions
n3:9286344
Subject Item
_:vb6524684
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n2:Context
rdf:value
nonadhesive dendritic cells produce dynamic actin-rich dendrites, instead of blebs, at their leading edge that cause these cell to become entangled with the ECM substrate during migration (Gunzer et al., 1997; Lämmermann et al., >>2008<<). Individual cells with high levels of attachment and cytoskeletal contractility develop mesenchymal migration, which involves focalized cell–matrix interactions and movement in a fibroblast-like manner (Kaye et al., 1971; Maaser et al.,
n2:mentions
n3:18451854
Subject Item
_:vb6524685
rdf:type
n2:Context
rdf:value
Individual cells with high levels of attachment and cytoskeletal contractility develop mesenchymal migration, which involves focalized cell–matrix interactions and movement in a fibroblast-like manner (Kaye et al., >>1971<<; Maaser et al., 1999; Grinnell, 2008).
n2:mentions
n3:5550533
Subject Item
_:vb6524686
rdf:type
n2:Context
rdf:value
cells with high levels of attachment and cytoskeletal contractility develop mesenchymal migration, which involves focalized cell–matrix interactions and movement in a fibroblast-like manner (Kaye et al., 1971; Maaser et al., >>1999<<; Grinnell, 2008). The migration of individual cells that transiently form and resolve cell–cell contacts while moving along a common track is termed chain migration or cell streaming (Davis and Trinkaus, 1981; Teddy and Kulesa, 2004).
n2:mentions
n3:10512851
Subject Item
_:vb6524687
rdf:type
n2:Context
rdf:value
with high levels of attachment and cytoskeletal contractility develop mesenchymal migration, which involves focalized cell–matrix interactions and movement in a fibroblast-like manner (Kaye et al., 1971; Maaser et al., 1999; Grinnell, >>2008<<). The migration of individual cells that transiently form and resolve cell–cell contacts while moving along a common track is termed chain migration or cell streaming (Davis and Trinkaus, 1981; Teddy and Kulesa, 2004).
n2:mentions
n3:19083673
Subject Item
_:vb6524688
rdf:type
n2:Context
rdf:value
The migration of individual cells that transiently form and resolve cell–cell contacts while moving along a common track is termed chain migration or cell streaming (Davis and Trinkaus, >>1981<<; Teddy and Kulesa, 2004).
n2:mentions
n3:7310293
Subject Item
_:vb6524689
rdf:type
n2:Context
rdf:value
The migration of individual cells that transiently form and resolve cell–cell contacts while moving along a common track is termed chain migration or cell streaming (Davis and Trinkaus, 1981; Teddy and Kulesa, >>2004<<). Finally, the maintenance of stringent cell–cell adhesions can lead to partial or complete silencing of migration activity in cells inside a group yet supports cytoskeletal activity at outward edges or at basal cell–substrate contacts.
n2:mentions
n3:15548586
Subject Item
_:vb6524690
rdf:type
n2:Context
rdf:value
The resulting collective migration occurs in the form of multicellular tubes, strands, irregularly shaped masses, or sheets (Vaughan and Trinkaus, >>1966<<; Friedl et al., 1995; Farooqui and Fenteany, 2005).
n2:mentions
n3:5956715
Subject Item
_:vb6524691
rdf:type
n2:Context
rdf:value
The resulting collective migration occurs in the form of multicellular tubes, strands, irregularly shaped masses, or sheets (Vaughan and Trinkaus, 1966; Friedl et al., >>1995<<; Farooqui and Fenteany, 2005).
n2:mentions
n3:7553628
Subject Item
_:vb6524692
rdf:type
n2:Context
rdf:value
The resulting collective migration occurs in the form of multicellular tubes, strands, irregularly shaped masses, or sheets (Vaughan and Trinkaus, 1966; Friedl et al., 1995; Farooqui and Fenteany, >>2005<<).
n2:mentions
n3:15585576
Subject Item
_:vb6524693
rdf:type
n2:Context
rdf:value
Most migration modes, although they can be observed in (mostly experimental) 2D environments, occur in vivo in the context of 3D tissue environments (Even-Ram and Yamada, >>2005<<). Conversely, in vivo, some migration modes are dedicated exclusively to 2D environments.
n2:mentions
n3:16112853
Subject Item
_:vb6524694
rdf:type
n2:Context
rdf:value
Epithelial keratocytes and keratinocytes migrate across flat 2D substrate using rapid spread-out cell gliding (Keren et al., >>2008<<) that, if cell–cell junctions between the cells remain intact, form a collectively migrating 2D cell sheet (Vaughan and Trinkaus, 1966; Farooqui and Fenteany, 2005).
n2:mentions
n3:18497816
Subject Item
_:vb6524695
rdf:type
n2:Context
rdf:value
keratinocytes migrate across flat 2D substrate using rapid spread-out cell gliding (Keren et al., 2008) that, if cell–cell junctions between the cells remain intact, form a collectively migrating 2D cell sheet (Vaughan and Trinkaus, >>1966<<; Farooqui and Fenteany, 2005).
n2:mentions
n3:5956715
Subject Item
_:vb6524696
rdf:type
n2:Context
rdf:value
flat 2D substrate using rapid spread-out cell gliding (Keren et al., 2008) that, if cell–cell junctions between the cells remain intact, form a collectively migrating 2D cell sheet (Vaughan and Trinkaus, 1966; Farooqui and Fenteany, >>2005<<). In different cell types, these modes of migration are associated with different efficiencies yielding varying migration speeds, such as the fast migratory scanning of single leukocytes, the relatively slow invasive migration of
n2:mentions
n3:15585576
Subject Item
_:vb6524697
rdf:type
n2:Context
rdf:value
the fast migratory scanning of single leukocytes, the relatively slow invasive migration of fibroblasts into provisorial wound matrix, or, at the slowest end, the collective migration during organ formation (Table I; Friedl et al., 1998b).
n2:mentions
n3:9858334
Subject Item
_:vb6524698
rdf:type
n2:Context
rdf:value
cell migration is essential in building, shaping, and remodeling complex tissues and tissue compartments, such as epithelia, ducts, glands, and vessels, but also contributes to cancer progression by local invasion (Alexander et al., >>2008<<; Friedl and Gilmour, 2009).
n2:mentions
n3:18987875
Subject Item
_:vb6524699
rdf:type
n2:Context
rdf:value
in building, shaping, and remodeling complex tissues and tissue compartments, such as epithelia, ducts, glands, and vessels, but also contributes to cancer progression by local invasion (Alexander et al., 2008; Friedl and Gilmour, >>2009<<). In contrast, single-cell migration allows cells either to cover local distances and integrate into tissues, such as neural crest cell migration, or to move from one location in the body to another and fulfill effector functions, such as
n2:mentions
n3:19546857
Subject Item
_:vb6524700
rdf:type
n2:Context
rdf:value
allows cells either to cover local distances and integrate into tissues, such as neural crest cell migration, or to move from one location in the body to another and fulfill effector functions, such as immune cell trafficking (Friedl, >>2004<<; Teddy and Kulesa, 2004; Lämmermann and Sixt, 2009). The latter process is recapitulated during cancer metastasis to distant sites (Thiery, 2002).
n2:mentions
n3:15037300
Subject Item
_:vb6524701
rdf:type
n2:Context
rdf:value
local distances and integrate into tissues, such as neural crest cell migration, or to move from one location in the body to another and fulfill effector functions, such as immune cell trafficking (Friedl, 2004; Teddy and Kulesa, >>2004<<; Lämmermann and Sixt, 2009). The latter process is recapitulated during cancer metastasis to distant sites (Thiery, 2002).
n2:mentions
n3:15548586
Subject Item
_:vb6524702
rdf:type
n2:Context
rdf:value
into tissues, such as neural crest cell migration, or to move from one location in the body to another and fulfill effector functions, such as immune cell trafficking (Friedl, 2004; Teddy and Kulesa, 2004; Lämmermann and Sixt, >>2009<<). The latter process is recapitulated during cancer metastasis to distant sites (Thiery, 2002).
n2:mentions
n3:19523798
Subject Item
_:vb6524703
rdf:type
n2:Context
rdf:value
The latter process is recapitulated during cancer metastasis to distant sites (Thiery, >>2002<<). Although not all molecular determinants of each migration mode are fully understood, some key parameters have been identified as “checkpoints” to either maintain a given migration type, or, by an increase or decrease of activity,
n2:mentions
n3:12189386
Subject Item
_:vb6524704
rdf:type
n5:Section
dc:title
determinants of cell migration
n5:contains
_:vb6524708 _:vb6524709 _:vb6524710 _:vb6524711 _:vb6524705 _:vb6524706 _:vb6524707 _:vb6524716 _:vb6524717 _:vb6524712 _:vb6524713 _:vb6524714 _:vb6524715
Subject Item
_:vb6524705
rdf:type
n2:Context
rdf:value
The common process underlying all migration modes of nucleated mammalian cells is polarized actomyosin-driven shape change of the cell body (Lauffenburger and Horwitz, >>1996<<; Ridley et al., 2003; Keren et al., 2008).
n2:mentions
n3:8608589
Subject Item
_:vb6524706
rdf:type
n2:Context
rdf:value
The common process underlying all migration modes of nucleated mammalian cells is polarized actomyosin-driven shape change of the cell body (Lauffenburger and Horwitz, 1996; Ridley et al., >>2003<<; Keren et al., 2008). This basic program is regulated and “shaped” by several distinct yet interdependent physical and molecular parameters of the tissue and the cell itself that together determine how a cell migrates (Fig.
n2:mentions
n3:14657486
Subject Item
_:vb6524707
rdf:type
n2:Context
rdf:value
The common process underlying all migration modes of nucleated mammalian cells is polarized actomyosin-driven shape change of the cell body (Lauffenburger and Horwitz, 1996; Ridley et al., 2003; Keren et al., >>2008<<). This basic program is regulated and “shaped” by several distinct yet interdependent physical and molecular parameters of the tissue and the cell itself that together determine how a cell migrates (Fig.
n2:mentions
n3:18497816
Subject Item
_:vb6524708
rdf:type
n2:Context
rdf:value
to environmental determinants, the actomyosin cytoskeleton adapts in a dynamic manner and generates different geometries in space and time, ranging from flat and spread out to roundish, elongated, or multipolar shapes (Grinnell, >>2008<<; Keren et al., 2008).
n2:mentions
n3:19083673
Subject Item
_:vb6524709
rdf:type
n2:Context
rdf:value
determinants, the actomyosin cytoskeleton adapts in a dynamic manner and generates different geometries in space and time, ranging from flat and spread out to roundish, elongated, or multipolar shapes (Grinnell, 2008; Keren et al., >>2008<<). To transmit actomyosin-driven forces to surrounding tissue structures, the cell either develops actin-polymerization–driven protrusions that bind to adhesion sites of the tissue through adhesion receptors (Yamada et al., 2003), or it
n2:mentions
n3:18497816
Subject Item
_:vb6524710
rdf:type
n2:Context
rdf:value
To transmit actomyosin-driven forces to surrounding tissue structures, the cell either develops actin-polymerization–driven protrusions that bind to adhesion sites of the tissue through adhesion receptors (Yamada et al., >>2003<<), or it utilizes poorly adhesive intercalation and propulsion (Paluch et al., 2006a).
n2:mentions
n3:12886449
Subject Item
_:vb6524711
rdf:type
n2:Context
rdf:value
the cell either develops actin-polymerization–driven protrusions that bind to adhesion sites of the tissue through adhesion receptors (Yamada et al., 2003), or it utilizes poorly adhesive intercalation and propulsion (Paluch et al., 2006a). In both cases, subsequent to leading edge protrusion, actomyosin contraction leads to retraction of the cell rear and translocation of the cell body (Paluch et al., 2006a; Lämmermann and Sixt, 2009).
n2:mentions
n3:16325405
Subject Item
_:vb6524712
rdf:type
n2:Context
rdf:value
In both cases, subsequent to leading edge protrusion, actomyosin contraction leads to retraction of the cell rear and translocation of the cell body (Paluch et al., 2006a; Lämmermann and Sixt, 2009).
n2:mentions
n3:16325405
Subject Item
_:vb6524713
rdf:type
n2:Context
rdf:value
In both cases, subsequent to leading edge protrusion, actomyosin contraction leads to retraction of the cell rear and translocation of the cell body (Paluch et al., 2006a; Lämmermann and Sixt, >>2009<<). The cyclic repetition of protrusion, interaction with the extracellular environment, and retraction of the cell rear result in cell movement that, depending on the molecular repertoire of the cell, yields distinct migratory modes
n2:mentions
n3:19523798
Subject Item
_:vb6524714
rdf:type
n2:Context
rdf:value
protrusion, interaction with the extracellular environment, and retraction of the cell rear result in cell movement that, depending on the molecular repertoire of the cell, yields distinct migratory modes (Lauffenburger and Horwitz, >>1996<<; Friedl and Wolf, 2009).
n2:mentions
n3:8608589
Subject Item
_:vb6524715
rdf:type
n2:Context
rdf:value
with the extracellular environment, and retraction of the cell rear result in cell movement that, depending on the molecular repertoire of the cell, yields distinct migratory modes (Lauffenburger and Horwitz, 1996; Friedl and Wolf, >>2009<<). Additional parameters impacting the type and efficiency of cell migration are the availability of surface proteases that remodel the surrounding tissue (Wolf and Friedl, 2009), and whether the cells retain stringent, loose, or no
n2:mentions
n3:19153672
Subject Item
_:vb6524716
rdf:type
n2:Context
rdf:value
Additional parameters impacting the type and efficiency of cell migration are the availability of surface proteases that remodel the surrounding tissue (Wolf and Friedl, >>2009<<), and whether the cells retain stringent, loose, or no cell–cell junctions (Friedl and Gilmour, 2009).
n2:mentions
n3:18600304
Subject Item
_:vb6524717
rdf:type
n2:Context
rdf:value
type and efficiency of cell migration are the availability of surface proteases that remodel the surrounding tissue (Wolf and Friedl, 2009), and whether the cells retain stringent, loose, or no cell–cell junctions (Friedl and Gilmour, >>2009<<).
n2:mentions
n3:19546857
Subject Item
_:vb6524718
rdf:type
n5:Section
dc:title
ecm determinants
n5:contains
_:vb6524748 _:vb6524749 _:vb6524750 _:vb6524744 _:vb6524745 _:vb6524746 _:vb6524747 _:vb6524740 _:vb6524741 _:vb6524742 _:vb6524743 _:vb6524736 _:vb6524737 _:vb6524738 _:vb6524739 _:vb6524732 _:vb6524733 _:vb6524734 _:vb6524735 _:vb6524728 _:vb6524729 _:vb6524730 _:vb6524731 _:vb6524724 _:vb6524725 _:vb6524726 _:vb6524727 _:vb6524720 _:vb6524721 _:vb6524722 _:vb6524723 _:vb6524719
Subject Item
_:vb6524719
rdf:type
n2:Context
rdf:value
Cell migration across 2D surfaces occurs during reepithelialization of wounds or the scanning of leukocytes along the inner blood vessel wall or inner epithelial surfaces (Farooqui and Fenteany, >>2005<<). Hallmarks of 2D migration are the requirement of unilateral adhesion to the substrate, which provides stable-enough but transient attachment; a flattened, spread-out cell morphology guided by a leading lamellipod; and, due to the flat
n2:mentions
n3:15585576
Subject Item
_:vb6524720
rdf:type
n2:Context
rdf:value
substrate, which provides stable-enough but transient attachment; a flattened, spread-out cell morphology guided by a leading lamellipod; and, due to the flat geometry of the substrate, a largely barrier-free migration (Ridley et al., >>2003<<; Farooqui and Fenteany, 2005; Keren et al., 2008; Vitorino and Meyer, 2008).
n2:mentions
n3:14657486
Subject Item
_:vb6524721
rdf:type
n2:Context
rdf:value
but transient attachment; a flattened, spread-out cell morphology guided by a leading lamellipod; and, due to the flat geometry of the substrate, a largely barrier-free migration (Ridley et al., 2003; Farooqui and Fenteany, >>2005<<; Keren et al., 2008; Vitorino and Meyer, 2008).
n2:mentions
n3:15585576
Subject Item
_:vb6524722
rdf:type
n2:Context
rdf:value
attachment; a flattened, spread-out cell morphology guided by a leading lamellipod; and, due to the flat geometry of the substrate, a largely barrier-free migration (Ridley et al., 2003; Farooqui and Fenteany, 2005; Keren et al., >>2008<<; Vitorino and Meyer, 2008).
n2:mentions
n3:18497816
Subject Item
_:vb6524723
rdf:type
n2:Context
rdf:value
spread-out cell morphology guided by a leading lamellipod; and, due to the flat geometry of the substrate, a largely barrier-free migration (Ridley et al., 2003; Farooqui and Fenteany, 2005; Keren et al., 2008; Vitorino and Meyer, >>2008<<). In contrast, when cells move through 3D interstitial tissue consisting of a network of interwoven collagen fibers, which impose space limitations against the moving cell body, their morphology undergoes characteristic changes.
n2:mentions
n3:19056882
Subject Item
_:vb6524724
rdf:type
n2:Context
rdf:value
tiplike cylindrical pseudopodia that orient in three dimensions; and third, the cell either deforms its shape to accommodate small tissue gaps or executes remodeling of the ECM structure by pericellular proteolysis (Maaser et al., >>1999<<; Wolf et al., 2003a; Jiang and Grinnell, 2005).
n2:mentions
n3:10512851
Subject Item
_:vb6524725
rdf:type
n2:Context
rdf:value
pseudopodia that orient in three dimensions; and third, the cell either deforms its shape to accommodate small tissue gaps or executes remodeling of the ECM structure by pericellular proteolysis (Maaser et al., 1999; Wolf et al., 2003a; Jiang and Grinnell, 2005).
n2:mentions
n3:12527751
Subject Item
_:vb6524726
rdf:type
n2:Context
rdf:value
in three dimensions; and third, the cell either deforms its shape to accommodate small tissue gaps or executes remodeling of the ECM structure by pericellular proteolysis (Maaser et al., 1999; Wolf et al., 2003a; Jiang and Grinnell, >>2005<<).
n2:mentions
n3:16107563
Subject Item
_:vb6524727
rdf:type
n2:Context
rdf:value
If the tissue gaps exceed the cell size, migration rates decrease (Haston et al., >>1982<<; Harley et al., 2008) because of a loss of most cell–fiber interactions until only very few or even a single fiber remain engaged with the cell body; the latter is termed “1D” migration (Doyle et al., 2009).
n2:mentions
n3:7085756
Subject Item
_:vb6524728
rdf:type
n2:Context
rdf:value
If the tissue gaps exceed the cell size, migration rates decrease (Haston et al., 1982; Harley et al., >>2008<<) because of a loss of most cell–fiber interactions until only very few or even a single fiber remain engaged with the cell body; the latter is termed “1D” migration (Doyle et al., 2009).
n2:mentions
n3:18621811
Subject Item
_:vb6524729
rdf:type
n2:Context
rdf:value
decrease (Haston et al., 1982; Harley et al., 2008) because of a loss of most cell–fiber interactions until only very few or even a single fiber remain engaged with the cell body; the latter is termed “1D” migration (Doyle et al., >>2009<<). Conversely, if pores range below the cell diameter, cells slow down and eventually may become trapped due to the physical hindrance (unpublished data; Haston et al., 1982; Harley et al., 2008).
n2:mentions
n3:19221195
Subject Item
_:vb6524730
rdf:type
n2:Context
rdf:value
Conversely, if pores range below the cell diameter, cells slow down and eventually may become trapped due to the physical hindrance (unpublished data; Haston et al., >>1982<<; Harley et al., 2008).
n2:mentions
n3:7085756
Subject Item
_:vb6524731
rdf:type
n2:Context
rdf:value
Conversely, if pores range below the cell diameter, cells slow down and eventually may become trapped due to the physical hindrance (unpublished data; Haston et al., 1982; Harley et al., >>2008<<). In response to extracellular confinement, migrating cells elongate to a spindle-like shape and thereby stretch and reduce their cell diameter, whereas large pore sizes favor cell rounding, a hallmark of amoeboid migration (unpublished
n2:mentions
n3:18621811
Subject Item
_:vb6524732
rdf:type
n2:Context
rdf:value
the cell and its most rigid compartment, the nucleus, is controlled by nuclear lamins A/C, which mechanically stabilize the nuclear membrane and potentially impact the minimum tissue gaps that can be transmigrated (Lammerding et al., >>2006<<; Dahl et al., 2008).
n2:mentions
n3:16825190
Subject Item
_:vb6524733
rdf:type
n2:Context
rdf:value
rigid compartment, the nucleus, is controlled by nuclear lamins A/C, which mechanically stabilize the nuclear membrane and potentially impact the minimum tissue gaps that can be transmigrated (Lammerding et al., 2006; Dahl et al., >>2008<<). Besides shape adaptation, cells that can proteolytically cleave ECM structures counteract physical hindrance by enlarging pores and forming trails of variable caliber so they match their own diameters (Wolf et al., 2007).
n2:mentions
n3:18535268
Subject Item
_:vb6524734
rdf:type
n2:Context
rdf:value
Besides shape adaptation, cells that can proteolytically cleave ECM structures counteract physical hindrance by enlarging pores and forming trails of variable caliber so they match their own diameters (Wolf et al., >>2007<<). Thus, the ability of the cell to deform relative to the available space and to remodel tissues through proteolysis determines both the mode and efficiency of migration in 3D ECM.
n2:mentions
n3:17618273
Subject Item
_:vb6524735
rdf:type
n2:Context
rdf:value
depends on molecular properties of the tissue, including collagen content, fiber thickness, and the extent of intrafibrillar cross-links, which define the stability and deformability of the tissue scaffold (Shoulders and Raines, >>2009<<). Cells detect matrix rigidity via integrin-mediated adhesions and downstream mechanosensor protein signaling (i.e., via talin and p130CAS; Giannone and Sheetz, 2006).
n2:mentions
n3:19344236
Subject Item
_:vb6524736
rdf:type
n2:Context
rdf:value
Cells detect matrix rigidity via integrin-mediated adhesions and downstream mechanosensor protein signaling (i.e., via talin and p130CAS; Giannone and Sheetz, >>2006<<). Increased substrate stiffness reinforces cell protrusions at outward edges so that focal adhesions form and become reinforced by RhoA-mediated actomyosin contraction, ultimately leading to cell spreading, the generation of high-traction
n2:mentions
n3:16529933
Subject Item
_:vb6524737
rdf:type
n2:Context
rdf:value
at outward edges so that focal adhesions form and become reinforced by RhoA-mediated actomyosin contraction, ultimately leading to cell spreading, the generation of high-traction force, and elongated cell movement (Peyton et al., >>2008<<; Ulrich et al., 2009). Conversely, soft matrix does not reinforce focal adhesion formation and cytoskeletal contractility; rather, it supports cell rounding (Ulrich et al., 2009).
n2:mentions
n3:18342366
Subject Item
_:vb6524738
rdf:type
n2:Context
rdf:value
so that focal adhesions form and become reinforced by RhoA-mediated actomyosin contraction, ultimately leading to cell spreading, the generation of high-traction force, and elongated cell movement (Peyton et al., 2008; Ulrich et al., >>2009<<). Conversely, soft matrix does not reinforce focal adhesion formation and cytoskeletal contractility; rather, it supports cell rounding (Ulrich et al., 2009).
n2:mentions
n3:19435897
Subject Item
_:vb6524739
rdf:type
n2:Context
rdf:value
Conversely, soft matrix does not reinforce focal adhesion formation and cytoskeletal contractility; rather, it supports cell rounding (Ulrich et al., >>2009<<). Consequently, matrix rigidity stimulates directed cell migration, similar to chemotaxis, so that cells tend to migrate toward substrate of greater stiffness, a process termed durotaxis (Lo et al., 2000; Li et al., 2005; Isenberg et al.,
n2:mentions
n3:19435897
Subject Item
_:vb6524740
rdf:type
n2:Context
rdf:value
Consequently, matrix rigidity stimulates directed cell migration, similar to chemotaxis, so that cells tend to migrate toward substrate of greater stiffness, a process termed durotaxis (Lo et al., >>2000<<; Li et al., 2005; Isenberg et al., 2009).
n2:mentions
n3:10866943
Subject Item
_:vb6524741
rdf:type
n2:Context
rdf:value
Consequently, matrix rigidity stimulates directed cell migration, similar to chemotaxis, so that cells tend to migrate toward substrate of greater stiffness, a process termed durotaxis (Lo et al., 2000; Li et al., >>2005<<; Isenberg et al., 2009).
n2:mentions
n3:16004568
Subject Item
_:vb6524742
rdf:type
n2:Context
rdf:value
matrix rigidity stimulates directed cell migration, similar to chemotaxis, so that cells tend to migrate toward substrate of greater stiffness, a process termed durotaxis (Lo et al., 2000; Li et al., 2005; Isenberg et al., >>2009<<).
n2:mentions
n3:19720019
Subject Item
_:vb6524743
rdf:type
n2:Context
rdf:value
Connective tissue comprises a range of physical textures, ranging from loose and random to highly aligned structures (Petrie et al., >>2009<<; Wolf et al., 2009).
n2:mentions
n3:19603038
Subject Item
_:vb6524744
rdf:type
n2:Context
rdf:value
mobile cells show a tendency to align in parallel along oriented structural discontinuities, such as at interfaces of muscle fibers, blood vessels, or ECM fiber strands and patterns created by the cells themselves (Provenzano et al., >>2008<<; Petrie et al., 2009). Contact guidance along such structures is mediated by mechanosensory integrins that, together with Rho/ROCK-mediated cytoskeletal stiffening, provide directional persistence (Dickinson et al., 1994; Provenzano et al.
n2:mentions
n3:18775961
Subject Item
_:vb6524745
rdf:type
n2:Context
rdf:value
tendency to align in parallel along oriented structural discontinuities, such as at interfaces of muscle fibers, blood vessels, or ECM fiber strands and patterns created by the cells themselves (Provenzano et al., 2008; Petrie et al., >>2009<<). Contact guidance along such structures is mediated by mechanosensory integrins that, together with Rho/ROCK-mediated cytoskeletal stiffening, provide directional persistence (Dickinson et al., 1994; Provenzano et al., 2008; Petrie et al.
n2:mentions
n3:19603038
Subject Item
_:vb6524746
rdf:type
n2:Context
rdf:value
Contact guidance along such structures is mediated by mechanosensory integrins that, together with Rho/ROCK-mediated cytoskeletal stiffening, provide directional persistence (Dickinson et al., >>1994<<; Provenzano et al., 2008; Petrie et al., 2009).
n2:mentions
n3:7998680
Subject Item
_:vb6524747
rdf:type
n2:Context
rdf:value
Contact guidance along such structures is mediated by mechanosensory integrins that, together with Rho/ROCK-mediated cytoskeletal stiffening, provide directional persistence (Dickinson et al., 1994; Provenzano et al., >>2008<<; Petrie et al., 2009).
n2:mentions
n3:18775961
Subject Item
_:vb6524748
rdf:type
n2:Context
rdf:value
guidance along such structures is mediated by mechanosensory integrins that, together with Rho/ROCK-mediated cytoskeletal stiffening, provide directional persistence (Dickinson et al., 1994; Provenzano et al., 2008; Petrie et al., >>2009<<). Although aligned fiber orientation in collagen-rich ECM does not seemingly impact cell shape (Provenzano et al., 2008), it favors multicellular streaming in chainlike patterns in 3D tissue (Friedl and Wolf, 2009) and migration of 2D
n2:mentions
n3:19603038
Subject Item
_:vb6524749
rdf:type
n2:Context
rdf:value
Although aligned fiber orientation in collagen-rich ECM does not seemingly impact cell shape (Provenzano et al., >>2008<<), it favors multicellular streaming in chainlike patterns in 3D tissue (Friedl and Wolf, 2009) and migration of 2D cell sheets along tissue clefts (unpublished data).
n2:mentions
n3:18775961
Subject Item
_:vb6524750
rdf:type
n2:Context
rdf:value
Although aligned fiber orientation in collagen-rich ECM does not seemingly impact cell shape (Provenzano et al., 2008), it favors multicellular streaming in chainlike patterns in 3D tissue (Friedl and Wolf, >>2009<<) and migration of 2D cell sheets along tissue clefts (unpublished data).
n2:mentions
n3:19153672
Subject Item
_:vb6524751
rdf:type
n5:Section
dc:title
cell determinants
n5:contains
_:vb6524816 _:vb6524817 _:vb6524818 _:vb6524819 _:vb6524820 _:vb6524821 _:vb6524808 _:vb6524809 _:vb6524810 _:vb6524811 _:vb6524812 _:vb6524813 _:vb6524814 _:vb6524815 _:vb6524800 _:vb6524801 _:vb6524802 _:vb6524803 _:vb6524804 _:vb6524805 _:vb6524806 _:vb6524807 _:vb6524760 _:vb6524761 _:vb6524762 _:vb6524763 _:vb6524764 _:vb6524765 _:vb6524766 _:vb6524767 _:vb6524752 _:vb6524753 _:vb6524754 _:vb6524755 _:vb6524756 _:vb6524757 _:vb6524758 _:vb6524759 _:vb6524792 _:vb6524793 _:vb6524794 _:vb6524795 _:vb6524796 _:vb6524797 _:vb6524798 _:vb6524799 _:vb6524784 _:vb6524785 _:vb6524786 _:vb6524787 _:vb6524788 _:vb6524789 _:vb6524790 _:vb6524791 _:vb6524776 _:vb6524777 _:vb6524778 _:vb6524779 _:vb6524780 _:vb6524781 _:vb6524782 _:vb6524783 _:vb6524768 _:vb6524769 _:vb6524770 _:vb6524771 _:vb6524772 _:vb6524773 _:vb6524774 _:vb6524775
Subject Item
_:vb6524752
rdf:type
n2:Context
rdf:value
A key determinant of how cells move is whether cell–cell junctions are retained or not, resulting in either collective or single-cell migration, respectively (Vitorino and Meyer, >>2008<<; Friedl and Gilmour, 2009).
n2:mentions
n3:19056882
Subject Item
_:vb6524753
rdf:type
n2:Context
rdf:value
A key determinant of how cells move is whether cell–cell junctions are retained or not, resulting in either collective or single-cell migration, respectively (Vitorino and Meyer, 2008; Friedl and Gilmour, >>2009<<). Cell–cell adhesion is mainly mediated by cadherins, including E-cadherin in epithelial cells, VE-cadherin in endothelial cells, and N-cadherin in stromal cells (Ewald et al., 2008; Vitorino and Meyer, 2008; Friedl and Gilmour, 2009).
n2:mentions
n3:19546857
Subject Item
_:vb6524754
rdf:type
n2:Context
rdf:value
Cell–cell adhesion is mainly mediated by cadherins, including E-cadherin in epithelial cells, VE-cadherin in endothelial cells, and N-cadherin in stromal cells (Ewald et al., >>2008<<; Vitorino and Meyer, 2008; Friedl and Gilmour, 2009).
n2:mentions
n3:18410732
Subject Item
_:vb6524755
rdf:type
n2:Context
rdf:value
Cell–cell adhesion is mainly mediated by cadherins, including E-cadherin in epithelial cells, VE-cadherin in endothelial cells, and N-cadherin in stromal cells (Ewald et al., 2008; Vitorino and Meyer, >>2008<<; Friedl and Gilmour, 2009).
n2:mentions
n3:19056882
Subject Item
_:vb6524756
rdf:type
n2:Context
rdf:value
Cell–cell adhesion is mainly mediated by cadherins, including E-cadherin in epithelial cells, VE-cadherin in endothelial cells, and N-cadherin in stromal cells (Ewald et al., 2008; Vitorino and Meyer, 2008; Friedl and Gilmour, >>2009<<). As opposed to individually migrating cells, during collective migration, the rear of the front cell retains intact cell–cell junctions to the successor cell, thereby mechanically holding the cells together and augmenting the efficiency
n2:mentions
n3:19546857
Subject Item
_:vb6524757
rdf:type
n2:Context
rdf:value
Coordinated cycles of protrusion and rear retraction of the front cells as well as of cells inside the group that engage with underlying substrate lead to movement as a multicellular unit (Farooqui and Fenteany, >>2005<<; Blanchard et al., 2009).
n2:mentions
n3:15585576
Subject Item
_:vb6524758
rdf:type
n2:Context
rdf:value
cycles of protrusion and rear retraction of the front cells as well as of cells inside the group that engage with underlying substrate lead to movement as a multicellular unit (Farooqui and Fenteany, 2005; Blanchard et al., >>2009<<). If cell–cell junctions are intermittent or less stable, multicellular streaming in a loose tail-to-head fashion results in the coordinated but individual migration of many cells through the tissue, with repetitive short-lived contacts
n2:mentions
n3:19412170
Subject Item
_:vb6524759
rdf:type
n2:Context
rdf:value
1; Teddy and Kulesa, >>2004<<). Lastly, if cell–cell contacts are absent, cells move independently in both speed and direction (Hegerfeldt et al., 2002).
n2:mentions
n3:15548586
Subject Item
_:vb6524760
rdf:type
n2:Context
rdf:value
Lastly, if cell–cell contacts are absent, cells move independently in both speed and direction (Hegerfeldt et al., >>2002<<). Thus, the presence of stable or transient cell–cell junctions, or their absence, determines whether collective translocation, cell streaming, or single-cell migration, respectively, is being generated.
n2:mentions
n3:11929834
Subject Item
_:vb6524761
rdf:type
n2:Context
rdf:value
The strength and turnover rates of cell attachments to the extracellular environment determine which cell shapes and forces are being generated during migration (Ridley et al., >>2003<<). Distinct cell types use adhesive strength over different magnitudes, ranging from strong adhesion by stromal fibroblasts or myoblasts (Huttenlocher et al., 1996), to moderate adhesion of epithelial and endothelial cells (Zhang et al.,
n2:mentions
n3:14657486
Subject Item
_:vb6524762
rdf:type
n2:Context
rdf:value
Distinct cell types use adhesive strength over different magnitudes, ranging from strong adhesion by stromal fibroblasts or myoblasts (Huttenlocher et al., >>1996<<), to moderate adhesion of epithelial and endothelial cells (Zhang et al., 2006; Schober et al., 2007), to weak adhesion forces of rapidly gliding fish keratocytes and crawling leukocytes (Friedl et al., 1998b; Keren et al., 2008;
n2:mentions
n3:8830782
Subject Item
_:vb6524763
rdf:type
n2:Context
rdf:value
Distinct cell types use adhesive strength over different magnitudes, ranging from strong adhesion by stromal fibroblasts or myoblasts (Huttenlocher et al., 1996), to moderate adhesion of epithelial and endothelial cells (Zhang et al., >>2006<<; Schober et al., 2007), to weak adhesion forces of rapidly gliding fish keratocytes and crawling leukocytes (Friedl et al., 1998b; Keren et al., 2008; Lämmermann et al., 2008).
n2:mentions
n3:16636073
Subject Item
_:vb6524764
rdf:type
n2:Context
rdf:value
adhesive strength over different magnitudes, ranging from strong adhesion by stromal fibroblasts or myoblasts (Huttenlocher et al., 1996), to moderate adhesion of epithelial and endothelial cells (Zhang et al., 2006; Schober et al., >>2007<<), to weak adhesion forces of rapidly gliding fish keratocytes and crawling leukocytes (Friedl et al., 1998b; Keren et al., 2008; Lämmermann et al., 2008).
n2:mentions
n3:17325207
Subject Item
_:vb6524765
rdf:type
n2:Context
rdf:value
(Huttenlocher et al., 1996), to moderate adhesion of epithelial and endothelial cells (Zhang et al., 2006; Schober et al., 2007), to weak adhesion forces of rapidly gliding fish keratocytes and crawling leukocytes (Friedl et al., 1998b; Keren et al., 2008; Lämmermann et al., 2008).
n2:mentions
n3:9858334
Subject Item
_:vb6524766
rdf:type
n2:Context
rdf:value
al., 1996), to moderate adhesion of epithelial and endothelial cells (Zhang et al., 2006; Schober et al., 2007), to weak adhesion forces of rapidly gliding fish keratocytes and crawling leukocytes (Friedl et al., 1998b; Keren et al., >>2008<<; Lämmermann et al., 2008).
n2:mentions
n3:18497816
Subject Item
_:vb6524767
rdf:type
n2:Context
rdf:value
adhesion of epithelial and endothelial cells (Zhang et al., 2006; Schober et al., 2007), to weak adhesion forces of rapidly gliding fish keratocytes and crawling leukocytes (Friedl et al., 1998b; Keren et al., 2008; Lämmermann et al., >>2008<<). High integrin expression levels are mandatory for high-attachment forces, but are also associated with relatively slow turnover of adhesion sites (Friedl et al., 1998b; Mc Henry et al., 2008) and, consequently, associated with slow
n2:mentions
n3:18451854
Subject Item
_:vb6524768
rdf:type
n2:Context
rdf:value
High integrin expression levels are mandatory for high-attachment forces, but are also associated with relatively slow turnover of adhesion sites (Friedl et al., 1998b; Mc Henry et al., 2008) and, consequently, associated with slow migration (Palecek et al., 1997).
n2:mentions
n3:9858334
Subject Item
_:vb6524769
rdf:type
n2:Context
rdf:value
High integrin expression levels are mandatory for high-attachment forces, but are also associated with relatively slow turnover of adhesion sites (Friedl et al., 1998b; Mc Henry et al., >>2008<<) and, consequently, associated with slow migration (Palecek et al., 1997).
n2:mentions
n3:17668446
Subject Item
_:vb6524770
rdf:type
n2:Context
rdf:value
levels are mandatory for high-attachment forces, but are also associated with relatively slow turnover of adhesion sites (Friedl et al., 1998b; Mc Henry et al., 2008) and, consequently, associated with slow migration (Palecek et al., >>1997<<). As an underlying mechanism, integrins and downstream mechanotransducing adaptors, such as p130CAS, become activated with increased mechanical tension and, in turn, further strengthen focal adhesions and actin stress fiber formation
n2:mentions
n3:9020360
Subject Item
_:vb6524771
rdf:type
n2:Context
rdf:value
mechanism, integrins and downstream mechanotransducing adaptors, such as p130CAS, become activated with increased mechanical tension and, in turn, further strengthen focal adhesions and actin stress fiber formation (Tamada et al., >>2004<<; Sawada et al., 2006).
n2:mentions
n3:15525532
Subject Item
_:vb6524772
rdf:type
n2:Context
rdf:value
and downstream mechanotransducing adaptors, such as p130CAS, become activated with increased mechanical tension and, in turn, further strengthen focal adhesions and actin stress fiber formation (Tamada et al., 2004; Sawada et al., >>2006<<). Strong cell–substrate adhesions thus promote cell contractility and the formation of elongated spread-out (2D) or spindle-shaped (3D) morphologies in many cell types, including fibroblasts, smooth muscle cells, and neoplastic cells
n2:mentions
n3:17129785
Subject Item
_:vb6524773
rdf:type
n2:Context
rdf:value
thus promote cell contractility and the formation of elongated spread-out (2D) or spindle-shaped (3D) morphologies in many cell types, including fibroblasts, smooth muscle cells, and neoplastic cells (Lauffenburger and Horwitz, >>1996<<; Friedl et al., 1998b; Maaser et al., 1999; Jiang and Grinnell, 2005).
n2:mentions
n3:8608589
Subject Item
_:vb6524774
rdf:type
n2:Context
rdf:value
contractility and the formation of elongated spread-out (2D) or spindle-shaped (3D) morphologies in many cell types, including fibroblasts, smooth muscle cells, and neoplastic cells (Lauffenburger and Horwitz, 1996; Friedl et al., 1998b; Maaser et al., 1999; Jiang and Grinnell, 2005).
n2:mentions
n3:9858334
Subject Item
_:vb6524775
rdf:type
n2:Context
rdf:value
the formation of elongated spread-out (2D) or spindle-shaped (3D) morphologies in many cell types, including fibroblasts, smooth muscle cells, and neoplastic cells (Lauffenburger and Horwitz, 1996; Friedl et al., 1998b; Maaser et al., >>1999<<; Jiang and Grinnell, 2005).
n2:mentions
n3:10512851
Subject Item
_:vb6524776
rdf:type
n2:Context
rdf:value
spread-out (2D) or spindle-shaped (3D) morphologies in many cell types, including fibroblasts, smooth muscle cells, and neoplastic cells (Lauffenburger and Horwitz, 1996; Friedl et al., 1998b; Maaser et al., 1999; Jiang and Grinnell, >>2005<<).
n2:mentions
n3:16107563
Subject Item
_:vb6524777
rdf:type
n2:Context
rdf:value
If cell adhesion is reduced to a moderate or low level, such as by interfering with the integrin-talin axis, focal adhesions and stress fibers do not form or do not reach full maturation (Zhang et al., >>2008<<). As a consequence, the cells convert to a less elongated or spread-out morphology, generate smaller lamellipodia and pseudopodia, and transmit limited adhesion strength toward the substrate (Zhang et al., 2008).
n2:mentions
n3:19160486
Subject Item
_:vb6524778
rdf:type
n2:Context
rdf:value
As a consequence, the cells convert to a less elongated or spread-out morphology, generate smaller lamellipodia and pseudopodia, and transmit limited adhesion strength toward the substrate (Zhang et al., >>2008<<). Rapidly moving lymphocytes and neutrophils that still adhere to ECM and other ligands but do not form focal adhesions or stress fibers constitutively use the pseudopodal amoeboid type of movement (Friedl et al., 1998a; Smith et al.,
n2:mentions
n3:19160486
Subject Item
_:vb6524779
rdf:type
n2:Context
rdf:value
Rapidly moving lymphocytes and neutrophils that still adhere to ECM and other ligands but do not form focal adhesions or stress fibers constitutively use the pseudopodal amoeboid type of movement (Friedl et al., 1998a; Smith et al., 2007).
n2:mentions
n3:9710211
Subject Item
_:vb6524780
rdf:type
n2:Context
rdf:value
Rapidly moving lymphocytes and neutrophils that still adhere to ECM and other ligands but do not form focal adhesions or stress fibers constitutively use the pseudopodal amoeboid type of movement (Friedl et al., 1998a; Smith et al., >>2007<<).
n2:mentions
n3:17218464
Subject Item
_:vb6524781
rdf:type
n2:Context
rdf:value
cells are unable to form unilateral attachments to 2D ECM substrate and thus fail to spread out, form lamellipodia, and move, whereas in a 3D environment, they move by amoeboid blebbing or dendritic intercalation (Haston et al., >>1982<<; Fackler and Grosse, 2008; Lämmermann and Sixt, 2009). Given such low adhesion capability, the mechanisms that generate force in this blebby (or dendritic) amoeboid translocation remain to be shown.
n2:mentions
n3:7085756
Subject Item
_:vb6524782
rdf:type
n2:Context
rdf:value
form unilateral attachments to 2D ECM substrate and thus fail to spread out, form lamellipodia, and move, whereas in a 3D environment, they move by amoeboid blebbing or dendritic intercalation (Haston et al., 1982; Fackler and Grosse, >>2008<<; Lämmermann and Sixt, 2009). Given such low adhesion capability, the mechanisms that generate force in this blebby (or dendritic) amoeboid translocation remain to be shown.
n2:mentions
n3:18541702
Subject Item
_:vb6524783
rdf:type
n2:Context
rdf:value
to 2D ECM substrate and thus fail to spread out, form lamellipodia, and move, whereas in a 3D environment, they move by amoeboid blebbing or dendritic intercalation (Haston et al., 1982; Fackler and Grosse, 2008; Lämmermann and Sixt, >>2009<<). Given such low adhesion capability, the mechanisms that generate force in this blebby (or dendritic) amoeboid translocation remain to be shown.
n2:mentions
n3:19523798
Subject Item
_:vb6524784
rdf:type
n2:Context
rdf:value
maintained by cortical actin provides high cytoskeletal rigidity locally, which allows mechanical intercalation between anterior parts of the cell with the surrounding tissue while the rear part of the cell retracts (Blaser et al., >>2006<<; Paluch et al., 2006a; Lämmermann and Sixt, 2009).
n2:mentions
n3:17084355
Subject Item
_:vb6524785
rdf:type
n2:Context
rdf:value
actin provides high cytoskeletal rigidity locally, which allows mechanical intercalation between anterior parts of the cell with the surrounding tissue while the rear part of the cell retracts (Blaser et al., 2006; Paluch et al., 2006a; Lämmermann and Sixt, 2009).
n2:mentions
n3:16325405
Subject Item
_:vb6524786
rdf:type
n2:Context
rdf:value
rigidity locally, which allows mechanical intercalation between anterior parts of the cell with the surrounding tissue while the rear part of the cell retracts (Blaser et al., 2006; Paluch et al., 2006a; Lämmermann and Sixt, >>2009<<).
n2:mentions
n3:19523798
Subject Item
_:vb6524787
rdf:type
n2:Context
rdf:value
First, the protrusion of pseudopodia, filopodia, and lamellipodia that adhere to cell and ECM substrates is directed by the small GTPases Rac and Cdc42 (Nobes and Hall, >>1999<<; Sanz-Moreno and Marshall, 2009).
n2:mentions
n3:10087266
Subject Item
_:vb6524788
rdf:type
n2:Context
rdf:value
First, the protrusion of pseudopodia, filopodia, and lamellipodia that adhere to cell and ECM substrates is directed by the small GTPases Rac and Cdc42 (Nobes and Hall, 1999; Sanz-Moreno and Marshall, >>2009<<). Consequently, high Rac activity conveys leading edge extension, elongated morphology, focal integrin engagement, and mesenchymal migration (Nobes and Hall, 1999; Sahai and Marshall, 2003; Sanz-Moreno et al., 2008). Second, bleb-like
n2:mentions
n3:19372747
Subject Item
_:vb6524789
rdf:type
n2:Context
rdf:value
Consequently, high Rac activity conveys leading edge extension, elongated morphology, focal integrin engagement, and mesenchymal migration (Nobes and Hall, >>1999<<; Sahai and Marshall, 2003; Sanz-Moreno et al., 2008).
n2:mentions
n3:10087266
Subject Item
_:vb6524790
rdf:type
n2:Context
rdf:value
Consequently, high Rac activity conveys leading edge extension, elongated morphology, focal integrin engagement, and mesenchymal migration (Nobes and Hall, 1999; Sahai and Marshall, >>2003<<; Sanz-Moreno et al., 2008).
n2:mentions
n3:12844144
Subject Item
_:vb6524791
rdf:type
n2:Context
rdf:value
Consequently, high Rac activity conveys leading edge extension, elongated morphology, focal integrin engagement, and mesenchymal migration (Nobes and Hall, 1999; Sahai and Marshall, 2003; Sanz-Moreno et al., >>2008<<). Second, bleb-like protrusions that contain cortical actin filaments are nonadhesive or poorly adhesive but contribute to lateral anchoring (“elbowing”) of the cell to tissue structures during actomyosin-mediated rear retraction (Paluch
n2:mentions
n3:18984162
Subject Item
_:vb6524792
rdf:type
n2:Context
rdf:value
protrusions that contain cortical actin filaments are nonadhesive or poorly adhesive but contribute to lateral anchoring (“elbowing”) of the cell to tissue structures during actomyosin-mediated rear retraction (Paluch et al., 2006a,b; Fackler and Grosse, 2008). In most cells, Rac-mediated protrusion of the leading edge is counterbalanced by Rho/ROCK signaling, which controls actomyosin-mediated retraction of the trailing edge.
n2:mentions
n3:16325405 n3:17145960
Subject Item
_:vb6524793
rdf:type
n2:Context
rdf:value
cortical actin filaments are nonadhesive or poorly adhesive but contribute to lateral anchoring (“elbowing”) of the cell to tissue structures during actomyosin-mediated rear retraction (Paluch et al., 2006a,b; Fackler and Grosse, >>2008<<). In most cells, Rac-mediated protrusion of the leading edge is counterbalanced by Rho/ROCK signaling, which controls actomyosin-mediated retraction of the trailing edge.
n2:mentions
n3:18541702
Subject Item
_:vb6524794
rdf:type
n2:Context
rdf:value
Together, they form a cyclic balance in distinct regions of the cell and contribute, concurrently, to the migration cycle (Ridley et al., >>2003<<; Sanz-Moreno and Marshall, 2009).
n2:mentions
n3:14657486
Subject Item
_:vb6524795
rdf:type
n2:Context
rdf:value
Together, they form a cyclic balance in distinct regions of the cell and contribute, concurrently, to the migration cycle (Ridley et al., 2003; Sanz-Moreno and Marshall, >>2009<<). High Rac activity generates cell elongation and mesenchymal migration, whereas active Rho in the presence of little or no Rac activity supports rounded cell shapes associated with amoeboid pseudopodal or blebbing migration, respectively
n2:mentions
n3:19372747
Subject Item
_:vb6524796
rdf:type
n2:Context
rdf:value
cell elongation and mesenchymal migration, whereas active Rho in the presence of little or no Rac activity supports rounded cell shapes associated with amoeboid pseudopodal or blebbing migration, respectively (Sahai and Marshall, >>2003<<; Sanz-Moreno et al., 2008).
n2:mentions
n3:12844144
Subject Item
_:vb6524797
rdf:type
n2:Context
rdf:value
migration, whereas active Rho in the presence of little or no Rac activity supports rounded cell shapes associated with amoeboid pseudopodal or blebbing migration, respectively (Sahai and Marshall, 2003; Sanz-Moreno et al., >>2008<<). Besides inducing cell protrusions, active Rac negatively regulates Rho/ROCK signaling and inhibits cell rounding, whereas active Rho/ROCK limits Rac, which inhibits cell extension and elongation (Sanz-Moreno et al., 2008).
n2:mentions
n3:18984162
Subject Item
_:vb6524798
rdf:type
n2:Context
rdf:value
Besides inducing cell protrusions, active Rac negatively regulates Rho/ROCK signaling and inhibits cell rounding, whereas active Rho/ROCK limits Rac, which inhibits cell extension and elongation (Sanz-Moreno et al., >>2008<<).
n2:mentions
n3:18984162
Subject Item
_:vb6524799
rdf:type
n2:Context
rdf:value
movement, whereas microtubules composed of deacetylated tubulin are subject to enhanced depolymerization by the microtubule-destabilizing factor stathmin and therefore support a rounded, amoeboid migration mode (Piperno et al., >>1987<<; Belletti et al., 2008; Berton et al., 2009).
n2:mentions
n3:2879846
Subject Item
_:vb6524800
rdf:type
n2:Context
rdf:value
microtubules composed of deacetylated tubulin are subject to enhanced depolymerization by the microtubule-destabilizing factor stathmin and therefore support a rounded, amoeboid migration mode (Piperno et al., 1987; Belletti et al., >>2008<<; Berton et al., 2009). Whether tubulin stability dictates cell shape by modulating to the balance between Rac and Rho activity or by other mechanisms, such as delivery of cargo or a direct mechanical function, is unknown.
n2:mentions
n3:18305103
Subject Item
_:vb6524801
rdf:type
n2:Context
rdf:value
of deacetylated tubulin are subject to enhanced depolymerization by the microtubule-destabilizing factor stathmin and therefore support a rounded, amoeboid migration mode (Piperno et al., 1987; Belletti et al., 2008; Berton et al., >>2009<<). Whether tubulin stability dictates cell shape by modulating to the balance between Rac and Rho activity or by other mechanisms, such as delivery of cargo or a direct mechanical function, is unknown.
n2:mentions
n3:19596789
Subject Item
_:vb6524802
rdf:type
n2:Context
rdf:value
A phase of actin polymerization–driven forward pushing of the plasma membrane is indispensible for leading edge protrusion, so it is included in most migration types (Lauffenburger and Horwitz, >>1996<<). In adhesive cells, pushing then leads to local adhesion, cytoskeletal anchorage, and, in a second phase, focal adhesion maturation and pulling on ECM substrate by actomyosin contraction (Ridley et al., 2003; Zhang et al., 2008). Pulling
n2:mentions
n3:8608589
Subject Item
_:vb6524803
rdf:type
n2:Context
rdf:value
In adhesive cells, pushing then leads to local adhesion, cytoskeletal anchorage, and, in a second phase, focal adhesion maturation and pulling on ECM substrate by actomyosin contraction (Ridley et al., >>2003<<; Zhang et al., 2008).
n2:mentions
n3:14657486
Subject Item
_:vb6524804
rdf:type
n2:Context
rdf:value
In adhesive cells, pushing then leads to local adhesion, cytoskeletal anchorage, and, in a second phase, focal adhesion maturation and pulling on ECM substrate by actomyosin contraction (Ridley et al., 2003; Zhang et al., >>2008<<). Pulling is proportional to adhesion strength and cytoskeletal contractility, such as in fibroblasts and myoblasts, to generate forces sufficient for substrate contraction (Beningo et al., 2001; Miron-Mendoza et al., 2008). In contrast,
n2:mentions
n3:19160486
Subject Item
_:vb6524805
rdf:type
n2:Context
rdf:value
Pulling is proportional to adhesion strength and cytoskeletal contractility, such as in fibroblasts and myoblasts, to generate forces sufficient for substrate contraction (Beningo et al., >>2001<<; Miron-Mendoza et al., 2008).
n2:mentions
n3:11352946
Subject Item
_:vb6524806
rdf:type
n2:Context
rdf:value
Pulling is proportional to adhesion strength and cytoskeletal contractility, such as in fibroblasts and myoblasts, to generate forces sufficient for substrate contraction (Beningo et al., 2001; Miron-Mendoza et al., >>2008<<). In contrast, if leading edge protrusion is coupled to low adhesion force, amoeboid pseudopodal migration occurs at very low traction force, as in moving neutrophils (Smith et al., 2007; Wang, Y.-L., personal communication). On the very
n2:mentions
n3:18321993
Subject Item
_:vb6524807
rdf:type
n2:Context
rdf:value
In contrast, if leading edge protrusion is coupled to low adhesion force, amoeboid pseudopodal migration occurs at very low traction force, as in moving neutrophils (Smith et al., >>2007<<; Wang, Y.-L., personal communication). On the very low end of adhesion and force generation, amoeboid blebbing cells tend to lack any attachment to 2D surfaces but rather float and oscillate on the spot (unpublished data; Paluch et al.,
n2:mentions
n3:17218464
Subject Item
_:vb6524808
rdf:type
n2:Context
rdf:value
On the very low end of adhesion and force generation, amoeboid blebbing cells tend to lack any attachment to 2D surfaces but rather float and oscillate on the spot (unpublished data; Paluch et al., 2006a). However, if included in a loose 3D ECM, such as a collagen matrix or matrigel, blebby cells that are deficient in pseudopodia or filopodia are still able to connect to the 3D substrate and generate movement, despite negligible
n2:mentions
n3:16325405
Subject Item
_:vb6524809
rdf:type
n2:Context
rdf:value
loose 3D ECM, such as a collagen matrix or matrigel, blebby cells that are deficient in pseudopodia or filopodia are still able to connect to the 3D substrate and generate movement, despite negligible attachment forces (Blaser et al., >>2006<<; Sanz-Moreno et al., 2008).
n2:mentions
n3:17084355
Subject Item
_:vb6524810
rdf:type
n2:Context
rdf:value
matrix or matrigel, blebby cells that are deficient in pseudopodia or filopodia are still able to connect to the 3D substrate and generate movement, despite negligible attachment forces (Blaser et al., 2006; Sanz-Moreno et al., >>2008<<). Thus, whereas mesenchymal migration depends on alternating pushing/pulling cycles, amoeboid migration is mechanically equally complex and comprises stronger pushing combined with a small or completely absent phase of adhesive pulling of
n2:mentions
n3:18984162
Subject Item
_:vb6524811
rdf:type
n2:Context
rdf:value
the 3D tissue, cells proteolytically remodel surrounding ECM and generate gaps, a hallmark of mesenchymal migration; otherwise, they move without engaging proteases by filling available spaces with their cell body (Friedl and Wolf, 2003a, 2009). In interstitial tissues, MT1-MMP is rate-limiting for collagen degradation, as it executes pericellular proteolysis of collagen fibers that physically impede the moving cell (Wolf et al., 2007; Sabeh et al., 2009).
n2:mentions
n3:14587300
Subject Item
_:vb6524812
rdf:type
n2:Context
rdf:value
3D tissue, cells proteolytically remodel surrounding ECM and generate gaps, a hallmark of mesenchymal migration; otherwise, they move without engaging proteases by filling available spaces with their cell body (Friedl and Wolf, 2003a, >>2009<<). In interstitial tissues, MT1-MMP is rate-limiting for collagen degradation, as it executes pericellular proteolysis of collagen fibers that physically impede the moving cell (Wolf et al., 2007; Sabeh et al., 2009).
n2:mentions
n3:19153672
Subject Item
_:vb6524813
rdf:type
n2:Context
rdf:value
In interstitial tissues, MT1-MMP is rate-limiting for collagen degradation, as it executes pericellular proteolysis of collagen fibers that physically impede the moving cell (Wolf et al., >>2007<<; Sabeh et al., 2009).
n2:mentions
n3:17618273
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_:vb6524814
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In interstitial tissues, MT1-MMP is rate-limiting for collagen degradation, as it executes pericellular proteolysis of collagen fibers that physically impede the moving cell (Wolf et al., 2007; Sabeh et al., >>2009<<). After cleavage, collagen fibers become displaced and realigned, which generates tubelike matrix gaps and trails of least resistance (Friedl and Wolf, 2008). In collagen-rich interstitial tissue, MT1-MMP is further involved in the
n2:mentions
n3:19332889
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_:vb6524815
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After cleavage, collagen fibers become displaced and realigned, which generates tubelike matrix gaps and trails of least resistance (Friedl and Wolf, >>2008<<). In collagen-rich interstitial tissue, MT1-MMP is further involved in the remodeling of already existing trails to even larger macrotracks, which then accommodate the collective invasion of multicellular strands (Wolf et al., 2007).
n2:mentions
n3:18794108
Subject Item
_:vb6524816
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In collagen-rich interstitial tissue, MT1-MMP is further involved in the remodeling of already existing trails to even larger macrotracks, which then accommodate the collective invasion of multicellular strands (Wolf et al., >>2007<<).
n2:mentions
n3:17618273
Subject Item
_:vb6524817
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In contrast to mesenchymal cells that are usually large, smaller amoeboid leukocytes employ much faster movement that lacks signs of pericellular proteolysis of the 3D interstitial substrate (Friedl and Wolf, 2003a). A mechanism of coping with narrow trails is cell deformation and squeezing through the pores so that extracellular structures imprint into the cell body and form local zones of cell compression (Wolf et al., 2003b).
n2:mentions
n3:14587300
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_:vb6524818
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A mechanism of coping with narrow trails is cell deformation and squeezing through the pores so that extracellular structures imprint into the cell body and form local zones of cell compression (Wolf et al., 2003b). If tissue densities are high, such as in basement membranes or dense connective tissue, inhibition of pericellular proteolysis cannot be compensated by shape change; instead, cell bodies get stuck in narrow pores (Sabeh et al., 2004,
n2:mentions
n3:12855577
Subject Item
_:vb6524819
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n2:Context
rdf:value
If tissue densities are high, such as in basement membranes or dense connective tissue, inhibition of pericellular proteolysis cannot be compensated by shape change; instead, cell bodies get stuck in narrow pores (Sabeh et al., >>2004<<, 2009). Likewise, if proteolytic macropatterning is prevented by protease inhibition, collective cell invasion is ablated and only individual amoeboid dissemination persists (Wolf et al., 2007).
n2:mentions
n3:15557125
Subject Item
_:vb6524820
rdf:type
n2:Context
rdf:value
If tissue densities are high, such as in basement membranes or dense connective tissue, inhibition of pericellular proteolysis cannot be compensated by shape change; instead, cell bodies get stuck in narrow pores (Sabeh et al., 2004, >>2009<<). Likewise, if proteolytic macropatterning is prevented by protease inhibition, collective cell invasion is ablated and only individual amoeboid dissemination persists (Wolf et al., 2007).
n2:mentions
n3:19332889
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_:vb6524821
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Likewise, if proteolytic macropatterning is prevented by protease inhibition, collective cell invasion is ablated and only individual amoeboid dissemination persists (Wolf et al., >>2007<<). Thus, proteolytic ECM remodeling is obligatory in tissues in which cell caliber and deformability fail to match available gaps and trails.
n2:mentions
n3:17618273
Subject Item
_:vb6524822
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n5:Section
dc:title
the tuning model
n5:contains
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Accordingly, integrin-mediated cell attachment to a deformable yet rigid substrate, but not to a soft substrate, enhances substrate tension and stiffness, which reinforces Rho-mediated traction force generation (Paszek et al., >>2005<<; Peyton et al., 2008; Ulrich et al., 2009).
n2:mentions
n3:16169468
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_:vb6524824
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n2:Context
rdf:value
integrin-mediated cell attachment to a deformable yet rigid substrate, but not to a soft substrate, enhances substrate tension and stiffness, which reinforces Rho-mediated traction force generation (Paszek et al., 2005; Peyton et al., >>2008<<; Ulrich et al., 2009). Likewise, traction force generation requires sufficient adhesion mediated by integrins, some Rac-mediated protrusion, and Rho-mediated cytoskeletal contraction (Rhee and Grinnell, 2006).
n2:mentions
n3:18342366
Subject Item
_:vb6524825
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n2:Context
rdf:value
attachment to a deformable yet rigid substrate, but not to a soft substrate, enhances substrate tension and stiffness, which reinforces Rho-mediated traction force generation (Paszek et al., 2005; Peyton et al., 2008; Ulrich et al., >>2009<<). Likewise, traction force generation requires sufficient adhesion mediated by integrins, some Rac-mediated protrusion, and Rho-mediated cytoskeletal contraction (Rhee and Grinnell, 2006).
n2:mentions
n3:19435897
Subject Item
_:vb6524826
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n2:Context
rdf:value
Likewise, traction force generation requires sufficient adhesion mediated by integrins, some Rac-mediated protrusion, and Rho-mediated cytoskeletal contraction (Rhee and Grinnell, >>2006<<). The physical tissue geometry is interdependent with protease acitivity of the cells; consequently, collective migration in 3D tissue depends on sufficiently high a priori porosity or the cell-mediated proteolytic generation of
n2:mentions
n3:16449192
Subject Item
_:vb6524827
rdf:type
n2:Context
rdf:value
geometry is interdependent with protease acitivity of the cells; consequently, collective migration in 3D tissue depends on sufficiently high a priori porosity or the cell-mediated proteolytic generation of macrotracks (Wolf et al., >>2007<<). Therefore, alteration of a given parameter has likely consequences for other interconnected determinants.
n2:mentions
n3:17618273
Subject Item
_:vb6524828
rdf:type
n5:Section
dc:title
plasticity: tuning the mode of migration
n5:contains
_:vb6524829 _:vb6524830 _:vb6524831 _:vb6524852 _:vb6524853 _:vb6524854 _:vb6524855 _:vb6524848 _:vb6524849 _:vb6524850 _:vb6524851 _:vb6524836 _:vb6524837 _:vb6524838 _:vb6524839 _:vb6524832 _:vb6524833 _:vb6524834 _:vb6524835 _:vb6524844 _:vb6524845 _:vb6524846 _:vb6524847 _:vb6524840 _:vb6524841 _:vb6524842 _:vb6524843
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state, each cell type preferentially employs a particular “default” migration type, such as leukocytes using amoeboid migration, stromal cells moving by a mesenchymal mode, or epithelial cell sheets moving collectively (Friedl, >>2004<<). However, in recent years, it has become clear that naturally occurring or experimentally induced modifications of either the environment or cell properties may result in striking adaptation reactions that alter the migration mode rather
n2:mentions
n3:15037300
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_:vb6524830
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n2:Context
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Because cell–cell junctions can form de novo and resolve again, individual and collective migration modes are interconvertible (Friedl and Gilmour, >>2009<<). If multicellular cohesion is weakened by the down-modulation of cell–cell junctions, individual cells detach from the multicellular unit which, dependent on the molecular repertoire and environment encountered, disseminate individually.
n2:mentions
n3:19546857
Subject Item
_:vb6524831
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n2:Context
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many developmental processes and in invasive cancers, and leads to the delamination of spindle-shaped cells that use integrin-mediated force generation for tissue invasion either as single cells or by multicellular streaming (Thiery, >>2002<<; Carmona-Fontaine et al., 2008). Collective-to-amoeboid transition occurs when the detached individual cells disseminate using amoeboid migration (Hegerfeldt et al., 2002; Wolf et al., 2007).
n2:mentions
n3:12189386
Subject Item
_:vb6524832
rdf:type
n2:Context
rdf:value
in invasive cancers, and leads to the delamination of spindle-shaped cells that use integrin-mediated force generation for tissue invasion either as single cells or by multicellular streaming (Thiery, 2002; Carmona-Fontaine et al., >>2008<<). Collective-to-amoeboid transition occurs when the detached individual cells disseminate using amoeboid migration (Hegerfeldt et al., 2002; Wolf et al., 2007).
n2:mentions
n3:19078960
Subject Item
_:vb6524833
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n2:Context
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Collective-to-amoeboid transition occurs when the detached individual cells disseminate using amoeboid migration (Hegerfeldt et al., >>2002<<; Wolf et al., 2007).
n2:mentions
n3:11929834
Subject Item
_:vb6524834
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n2:Context
rdf:value
Collective-to-amoeboid transition occurs when the detached individual cells disseminate using amoeboid migration (Hegerfeldt et al., 2002; Wolf et al., >>2007<<). Conversely, if individually moving cells up-regulate cell–cell adhesion molecules, then cell aggregation leads to individual-to-collective transition (Thiery, 2002).
n2:mentions
n3:17618273
Subject Item
_:vb6524835
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Conversely, if individually moving cells up-regulate cell–cell adhesion molecules, then cell aggregation leads to individual-to-collective transition (Thiery, >>2002<<).
n2:mentions
n3:12189386
Subject Item
_:vb6524836
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A central pathway controlling the interconversion between mesenchymal and rounded, amoeboid migration is the balance between Rac and Rho signaling (Sahai and Marshall, >>2003<<). In many experimental examples, mesenchymal-to-amoeboid transitions depend, directly or indirectly, on pathways that weaken Rac and/or strengthen Rho/ROCK signaling (Sanz-Moreno et al., 2008; Paňková et al., 2009; Sanz-Moreno and
n2:mentions
n3:12844144
Subject Item
_:vb6524837
rdf:type
n2:Context
rdf:value
In many experimental examples, mesenchymal-to-amoeboid transitions depend, directly or indirectly, on pathways that weaken Rac and/or strengthen Rho/ROCK signaling (Sanz-Moreno et al., >>2008<<; Paňková et al., 2009; Sanz-Moreno and Marshall, 2009).
n2:mentions
n3:18984162
Subject Item
_:vb6524838
rdf:type
n2:Context
rdf:value
experimental examples, mesenchymal-to-amoeboid transitions depend, directly or indirectly, on pathways that weaken Rac and/or strengthen Rho/ROCK signaling (Sanz-Moreno et al., 2008; Paňková et al., 2009; Sanz-Moreno and Marshall, >>2009<<). Thus, upstream pathways that suppress Rac activity induce this conversion, including the activation of the GTPase-activating protein (GAP) ARHGAP22, which directly inhibits Rac (Sanz-Moreno et al., 2008); inhibition of the
n2:mentions
n3:19372747
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_:vb6524839
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Thus, upstream pathways that suppress Rac activity induce this conversion, including the activation of the GTPase-activating protein (GAP) ARHGAP22, which directly inhibits Rac (Sanz-Moreno et al., >>2008<<); inhibition of the Rac-activating guanine nucleotide exchange factor DOCK3/NEDD9 or of the down-stream Rac effector and Rho inhibitor WAVE-II (Sanz-Moreno et al., 2008); interference with Rab5-mediated endocytosis and recycling of Rac to
n2:mentions
n3:18984162
Subject Item
_:vb6524840
rdf:type
n2:Context
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(GAP) ARHGAP22, which directly inhibits Rac (Sanz-Moreno et al., 2008); inhibition of the Rac-activating guanine nucleotide exchange factor DOCK3/NEDD9 or of the down-stream Rac effector and Rho inhibitor WAVE-II (Sanz-Moreno et al., >>2008<<); interference with Rab5-mediated endocytosis and recycling of Rac to cell protrusions (Palamidessi et al., 2008); and the inhibition of E3 ubiquitin ligase Smurf1, which enzymatically degrades Rho near the leading edge and thereby
n2:mentions
n3:18984162
Subject Item
_:vb6524841
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n2:Context
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nucleotide exchange factor DOCK3/NEDD9 or of the down-stream Rac effector and Rho inhibitor WAVE-II (Sanz-Moreno et al., 2008); interference with Rab5-mediated endocytosis and recycling of Rac to cell protrusions (Palamidessi et al., >>2008<<); and the inhibition of E3 ubiquitin ligase Smurf1, which enzymatically degrades Rho near the leading edge and thereby secures the dominance of Rac in cell protrusions (Sahai et al., 2007).
n2:mentions
n3:18614017
Subject Item
_:vb6524842
rdf:type
n2:Context
rdf:value
Rac to cell protrusions (Palamidessi et al., 2008); and the inhibition of E3 ubiquitin ligase Smurf1, which enzymatically degrades Rho near the leading edge and thereby secures the dominance of Rac in cell protrusions (Sahai et al., >>2007<<). Likewise, inhibition of chemokine-meditated Rac activation favors amoeboid movement in otherwise mesenchymal cells (Gérard et al., 2007).
n2:mentions
n3:17190792
Subject Item
_:vb6524843
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Likewise, inhibition of chemokine-meditated Rac activation favors amoeboid movement in otherwise mesenchymal cells (Gérard et al., >>2007<<). Pathways that activate Rho lead to mesenchymal-to-amoeboid transition, including inhibition of negative Rho regulators (e.g., p90RhoGAP) through an indirect, reactive oxygen species-dependent mechanism (Nimnual et al., 2003) or the
n2:mentions
n3:17353362
Subject Item
_:vb6524844
rdf:type
n2:Context
rdf:value
Pathways that activate Rho lead to mesenchymal-to-amoeboid transition, including inhibition of negative Rho regulators (e.g., p90RhoGAP) through an indirect, reactive oxygen species-dependent mechanism (Nimnual et al., >>2003<<) or the activation of Ephrin2A receptor tyrosine kinase signaling, which indirectly activates Rho (Parri et al., 2009).
n2:mentions
n3:12598902
Subject Item
_:vb6524845
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n2:Context
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Rho regulators (e.g., p90RhoGAP) through an indirect, reactive oxygen species-dependent mechanism (Nimnual et al., 2003) or the activation of Ephrin2A receptor tyrosine kinase signaling, which indirectly activates Rho (Parri et al., >>2009<<).
n2:mentions
n3:19244130
Subject Item
_:vb6524846
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n2:Context
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The transition from amoeboid myeloid precursor cells to adhesive elongated and contractile macrophages is initiated by the up-regulation and activation of β1, β2, and β3 integrins (McNally and Anderson, >>2002<<). Conversely, mesenchymal cells convert to amoeboid movement in experimental 3D matrices after limiting pathways that control focal adhesion formation, including inhibition of β1 integrin–mediated adhesion or of the tyrosine kinase cSrc
n2:mentions
n3:11839583
Subject Item
_:vb6524847
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n2:Context
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cells convert to amoeboid movement in experimental 3D matrices after limiting pathways that control focal adhesion formation, including inhibition of β1 integrin–mediated adhesion or of the tyrosine kinase cSrc (Carragher et al., >>2006<<; Zaman et al., 2006). Plasticity imposed by altered tissue architecture occurs when cells transit from a 2D interface into 3D tissue.
n2:mentions
n3:16652152
Subject Item
_:vb6524848
rdf:type
n2:Context
rdf:value
amoeboid movement in experimental 3D matrices after limiting pathways that control focal adhesion formation, including inhibition of β1 integrin–mediated adhesion or of the tyrosine kinase cSrc (Carragher et al., 2006; Zaman et al., >>2006<<). Plasticity imposed by altered tissue architecture occurs when cells transit from a 2D interface into 3D tissue.
n2:mentions
n3:16832052
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_:vb6524849
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The initial spread-out or cuboidal 2D phenotype then converts toward a spindle-shaped mesenchymal phenotype with vertical penetration and migration into the 3D matrix (Alt-Holland et al., >>2008<<). Lastly, in loose interstitial tissues with gaps that accommodate the cell body, the inhibition of surface protease activity causes a transition from protease-dependent mesenchymal migration to amoeboid migration involving shape change
n2:mentions
n3:18528437
Subject Item
_:vb6524850
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the cell body, the inhibition of surface protease activity causes a transition from protease-dependent mesenchymal migration to amoeboid migration involving shape change and squeezing without tissue remodeling (Wolf et al., 2003a, 2007).
n2:mentions
n3:12527751
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_:vb6524851
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the cell body, the inhibition of surface protease activity causes a transition from protease-dependent mesenchymal migration to amoeboid migration involving shape change and squeezing without tissue remodeling (Wolf et al., 2003a, >>2007<<).
n2:mentions
n3:17618273
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_:vb6524852
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These transitions of migration mode are best studied for cancer cells and likely contribute to the metastatic cascade (Friedl and Wolf, 2003b; Sanz-Moreno and Marshall, 2009), yet they are also relevant to cell migration and function in physiological contexts, such as the delamination of cells during morphogenesis and the distribution of stem cells or leukocytes in tissues and
n2:mentions
n3:12724734
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_:vb6524853
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These transitions of migration mode are best studied for cancer cells and likely contribute to the metastatic cascade (Friedl and Wolf, 2003b; Sanz-Moreno and Marshall, >>2009<<), yet they are also relevant to cell migration and function in physiological contexts, such as the delamination of cells during morphogenesis and the distribution of stem cells or leukocytes in tissues and organs (Blaser et al., 2006;
n2:mentions
n3:19372747
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_:vb6524854
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2009), yet they are also relevant to cell migration and function in physiological contexts, such as the delamination of cells during morphogenesis and the distribution of stem cells or leukocytes in tissues and organs (Blaser et al., >>2006<<; Lämmermann and Sixt, 2009).
n2:mentions
n3:17084355
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_:vb6524855
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to cell migration and function in physiological contexts, such as the delamination of cells during morphogenesis and the distribution of stem cells or leukocytes in tissues and organs (Blaser et al., 2006; Lämmermann and Sixt, >>2009<<).
n2:mentions
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44
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42
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20
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19
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18
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18
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17
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17
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16
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16
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15
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