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n4:pmcid: PMC0
bibo:doi: 10.1371%2Fjournal.pone.0054752
n8:contains: _:vb20450865 _:vb20450853 _:vb20450837 _:vb20450894

Subject Item: _:vb20450837
rdf:type: n8:Section
dc:title: introduction
n8:contains: _:vb20450848 _:vb20450849 _:vb20450850 _:vb20450851 _:vb20450852 _:vb20450838 _:vb20450839 _:vb20450840 _:vb20450841 _:vb20450842 _:vb20450843 _:vb20450844 _:vb20450845 _:vb20450846 _:vb20450847

Subject Item: _:vb20450838
rdf:type: n4:Context
rdf:value: Glioblastoma (GBM) is the most common form of malignant brain tumor; the current treatment of choice for patients with GBM involves surgery, radiotherapy and temozolomide [>>1<<]. Whereas this multimodality treatment approach prolongs survival, the vast majority of patients with GBM succumb to their disease within 1–2 years of diagnosis [1].
n4:mentions: n2:19269895

Subject Item: _:vb20450839
rdf:type: n4:Context
rdf:value: Whereas this multimodality treatment approach prolongs survival, the vast majority of patients with GBM succumb to their disease within 1–2 years of diagnosis [>>1<<]. Accounting for this poor survival is the presumed intrinsic resistance of GBM cells to standard cytotoxic agents. However, an additional barrier to successful therapy is the invasive propensity of GBM. The capacity of GBM cells to
n4:mentions: n2:19269895

Subject Item: _:vb20450840
rdf:type: n4:Context
rdf:value: have a number of in vitro properties in common with normal neural stem cells including continuous self-renewal; expression of stem cell related genes and the capacity to at least partial differentiate along neuronal and glial pathways [>>2<<], [3]. Moreover, when implanted in immuno-deficient mice GSCs form a highly invasive, phenotypically heterogeneous brain tumor [4].
n4:mentions: n2:15549107

Subject Item: _:vb20450841
rdf:type: n4:Context
rdf:value: a number of in vitro properties in common with normal neural stem cells including continuous self-renewal; expression of stem cell related genes and the capacity to at least partial differentiate along neuronal and glial pathways [2], [>>3<<]. Moreover, when implanted in immuno-deficient mice GSCs form a highly invasive, phenotypically heterogeneous brain tumor [4].
n4:mentions: n2:15466194

Subject Item: _:vb20450842
rdf:type: n4:Context
rdf:value: Moreover, when implanted in immuno-deficient mice GSCs form a highly invasive, phenotypically heterogeneous brain tumor [>>4<<]. Given the putative significance of GSCs in GBM development and progression, it has been generally assumed that they should also play a major role in determining GBM invasion into normal brain tissue.
n4:mentions: n2:14522905

Subject Item: _:vb20450843
rdf:type: n4:Context
rdf:value: The invasive activities of GSCs and non-GSCs have been compared and the mechanism investigated under standard in vitro conditions [>>5<<]. However, because invasion reflects an interaction between tumor cells and the surrounding normal tissue, it would seem that to understand the processes mediating GBM invasion it will be necessary to account for the brain microenvironment.
n4:mentions: n2:21371437

Subject Item: _:vb20450844
rdf:type: n4:Context
rdf:value: Whereas the parenchyma is composed of a variety of phenotypes, astrocytes are the most frequent non-neuronal cell type comprising approximately 50% of the human brain volume [>>6<<] and consequently are likely to represent the most frequent point of contact for tumor cells.
n4:mentions: n2:4633361

Subject Item: _:vb20450845
rdf:type: n4:Context
rdf:value: Astrocytes are a rich source of growth factors, cytokines and other bioactive molecules including proteases and their inhibitors [>>7<<], [8]. Moreover, they are intimately involved in the brain response to multiple forms of injury [9], [10]. Finally, astrocytes play a major role in the maintenance and remodeling of the brain extra-cellular matrix [9], [10], [11], [12].
n4:mentions: n2:14670989

Subject Item: _:vb20450846
rdf:type: n4:Context
rdf:value: Astrocytes are a rich source of growth factors, cytokines and other bioactive molecules including proteases and their inhibitors [7], [>>8<<]. Moreover, they are intimately involved in the brain response to multiple forms of injury [9], [10]. Finally, astrocytes play a major role in the maintenance and remodeling of the brain extra-cellular matrix [9], [10], [11], [12]. Thus,
n4:mentions: n2:7572280

Subject Item: _:vb20450847
rdf:type: n4:Context
rdf:value: Moreover, they are intimately involved in the brain response to multiple forms of injury [>>9<<], [10]. Finally, astrocytes play a major role in the maintenance and remodeling of the brain extra-cellular matrix [9], [10], [11], [12]. Thus, in an attempt to better simulate the in situ environment and to test the hypothesis that normal
n4:mentions: n2:20012068

Subject Item: _:vb20450848
rdf:type: n4:Context
rdf:value: Moreover, they are intimately involved in the brain response to multiple forms of injury [9], [>>10<<]. Finally, astrocytes play a major role in the maintenance and remodeling of the brain extra-cellular matrix [9], [10], [11], [12]. Thus, in an attempt to better simulate the in situ environment and to test the hypothesis that normal brain
n4:mentions: n2:12571445

Subject Item: _:vb20450849
rdf:type: n4:Context
rdf:value: Finally, astrocytes play a major role in the maintenance and remodeling of the brain extra-cellular matrix [>>9<<], [10], [11], [12].
n4:mentions: n2:20012068

Subject Item: _:vb20450850
rdf:type: n4:Context
rdf:value: Finally, astrocytes play a major role in the maintenance and remodeling of the brain extra-cellular matrix [9], [>>10<<], [11], [12].
n4:mentions: n2:12571445

Subject Item: _:vb20450851
rdf:type: n4:Context
rdf:value: Finally, astrocytes play a major role in the maintenance and remodeling of the brain extra-cellular matrix [9], [10], [>>11<<], [12]. Thus, in an attempt to better simulate the in situ environment and to test the hypothesis that normal brain cells influence GBM behavior, we have used co-culture conditions to define the effects of human astrocytes on GSC and
n4:mentions: n2:17387691

Subject Item: _:vb20450852
rdf:type: n4:Context
rdf:value: Finally, astrocytes play a major role in the maintenance and remodeling of the brain extra-cellular matrix [9], [10], [11], [>>12<<]. Thus, in an attempt to better simulate the in situ environment and to test the hypothesis that normal brain cells influence GBM behavior, we have used co-culture conditions to define the effects of human astrocytes on GSC and non-GSC
n4:mentions: n2:15094120

Subject Item: _:vb20450853
rdf:type: n8:Section
dc:title: materials and methods
n8:contains: _:vb20450864 _:vb20450854 _:vb20450855 _:vb20450856 _:vb20450857 _:vb20450858 _:vb20450859 _:vb20450860 _:vb20450861 _:vb20450862 _:vb20450863

Subject Item: _:vb20450854
rdf:type: n4:Context
rdf:value: The neurosphere forming cultures NSC11 [>>13<<] (kindly provided by Dr. Frederick Lang, M. D. Anderson Cancer Center) and GBAM1 [14] were isolated from human GBM surgical specimens as described previously [3].
n4:mentions: n2:19372578

Subject Item: _:vb20450855
rdf:type: n4:Context
rdf:value: Anderson Cancer Center) and GBAM1 [>>14<<] were isolated from human GBM surgical specimens as described previously [3].
n4:mentions: n2:19671863

Subject Item: _:vb20450856
rdf:type: n4:Context
rdf:value: Anderson Cancer Center) and GBAM1 [14] were isolated from human GBM surgical specimens as described previously [>>3<<]. Neurospheres were maintained in stem cell medium (DMEM/F-12, B27 supplement (Invitrogen) and bFGF and EGF (50 ng/ml each, R&D Systems)) and maintained at 37°C in an atmosphere of 5% CO2/5% O2. CD133+ cells were isolated from GBM
n4:mentions: n2:15466194

Subject Item: _:vb20450857
rdf:type: n4:Context
rdf:value: CD133+ cells were isolated from GBM neurosphere cultures by FACS as previously described [>>4<<], [13] and used as a source for the described experiments.
n4:mentions: n2:14522905

Subject Item: _:vb20450858
rdf:type: n4:Context
rdf:value: CD133+ cells were isolated from GBM neurosphere cultures by FACS as previously described [4], [>>13<<] and used as a source for the described experiments.
n4:mentions: n2:19372578

Subject Item: _:vb20450859
rdf:type: n4:Context
rdf:value: Both CD133+ cell cultures met the criteria for tumor stem-like cells [>>4<<] , [13], [14].
n4:mentions: n2:14522905

Subject Item: _:vb20450860
rdf:type: n4:Context
rdf:value: Both CD133+ cell cultures met the criteria for tumor stem-like cells [4] , [>>13<<], [14]. For use in an in vitro experiment, CD133+ neurosphere cultures (>90% CD133+ cells) were disaggregated [13] and seeded into poly-L-ornithine/laminin (po/ln; Sigma-Aldrich) coated culture dishes. Under these conditions GSCs grow as
n4:mentions: n2:19372578

Subject Item: _:vb20450861
rdf:type: n4:Context
rdf:value: Both CD133+ cell cultures met the criteria for tumor stem-like cells [4] , [13], [>>14<<]. For use in an in vitro experiment, CD133+ neurosphere cultures (>90% CD133+ cells) were disaggregated [13] and seeded into poly-L-ornithine/laminin (po/ln; Sigma-Aldrich) coated culture dishes. Under these conditions GSCs grow as an
n4:mentions: n2:19671863

Subject Item: _:vb20450862
rdf:type: n4:Context
rdf:value: For use in an in vitro experiment, CD133+ neurosphere cultures (>90% CD133+ cells) were disaggregated [>>13<<] and seeded into poly-L-ornithine/laminin (po/ln; Sigma-Aldrich) coated culture dishes.
n4:mentions: n2:19372578

Subject Item: _:vb20450863
rdf:type: n4:Context
rdf:value: Under these conditions GSCs grow as an adherent monolayer maintaining their CD133 expression [>>13<<] and stem-like characteristics [15].
n4:mentions: n2:19372578

Subject Item: _:vb20450864
rdf:type: n4:Context
rdf:value: Under these conditions GSCs grow as an adherent monolayer maintaining their CD133 expression [13] and stem-like characteristics [>>15<<]. To induce differentiation, CD133+ cells were exposed to DMEM/F-12 and 10% fetal bovine serum (FBS) for 10 days. Differentiation was defined as the loss of CD133 expression, the gain of expression of GFAP and/or β-III tubulin and cell
n4:mentions: n2:19497285

Subject Item: _:vb20450865
rdf:type: n8:Section
dc:title: results
n8:contains: _:vb20450866 _:vb20450867 _:vb20450868 _:vb20450869 _:vb20450870 _:vb20450871 _:vb20450872 _:vb20450873 _:vb20450874 _:vb20450875 _:vb20450876 _:vb20450877 _:vb20450878 _:vb20450879 _:vb20450880 _:vb20450881 _:vb20450882 _:vb20450883 _:vb20450884 _:vb20450885 _:vb20450886 _:vb20450887 _:vb20450888 _:vb20450889 _:vb20450890 _:vb20450891 _:vb20450892 _:vb20450893

Subject Item: _:vb20450866
rdf:type: n4:Context
rdf:value: The NSC11 and GBAM1 CD133+ GSC cultures used in these studies met the criteria for tumor stem-like cells [>>4<<] including self-renewal, differentiation along glial and neuronal pathways, expression of stem cell related genes and formation of brain tumors when implanted in immunodeficient mice [13], [14].
n4:mentions: n2:14522905

Subject Item: _:vb20450867
rdf:type: n4:Context
rdf:value: met the criteria for tumor stem-like cells [4] including self-renewal, differentiation along glial and neuronal pathways, expression of stem cell related genes and formation of brain tumors when implanted in immunodeficient mice [>>13<<], [14]. To induce differentiation of the GSC lines, cells were exposed to DMEM/F-12 containing 10% FBS for 10 days, which resulted in the loss of CD133 expression, the gain of expression of GFAP and/or β-III tubulin and cell cycle arrest.
n4:mentions: n2:19372578

Subject Item: _:vb20450868
rdf:type: n4:Context
rdf:value: met the criteria for tumor stem-like cells [4] including self-renewal, differentiation along glial and neuronal pathways, expression of stem cell related genes and formation of brain tumors when implanted in immunodeficient mice [13], [>>14<<]. To induce differentiation of the GSC lines, cells were exposed to DMEM/F-12 containing 10% FBS for 10 days, which resulted in the loss of CD133 expression, the gain of expression of GFAP and/or β-III tubulin and cell cycle arrest.
n4:mentions: n2:19671863

Subject Item: _:vb20450869
rdf:type: n4:Context
rdf:value: For these studies the top membrane was coated with polyornithine/laminin (po/ln), which approximates the brain extra-cellular matrix [>>12<<]. For each cell type the invasion assay was performed using the corresponding growth media, i.e., for CD133+ cells: stem cell medium; CD133− cells: DMEM/F-12 with 10% FBS (see Methods). Under these conditions, the invasion capacity of
n4:mentions: n2:15094120

Subject Item: _:vb20450870
rdf:type: n4:Context
rdf:value: Of interest, addition of FBS, which is often used as an invasion stimulus in this assay [>>16<<] and is included in the media used in the analysis of CD133− cell invasion (Figure 1B), had no effect on CD133+ cell invasion (Figure 1A).
n4:mentions: n2:15576908

Subject Item: _:vb20450871
rdf:type: n4:Context
rdf:value: Of the hub genes within the network CCL2, CD44, ANXA1 and ANXA2 have been linked to cell migration/invasion [>>17<<], [18], [19], [20].
n4:mentions: n2:21486440

Subject Item: _:vb20450872
rdf:type: n4:Context
rdf:value: Of the hub genes within the network CCL2, CD44, ANXA1 and ANXA2 have been linked to cell migration/invasion [17], [>>18<<], [19], [20].
n4:mentions: n2:22024282

Subject Item: _:vb20450873
rdf:type: n4:Context
rdf:value: Of the hub genes within the network CCL2, CD44, ANXA1 and ANXA2 have been linked to cell migration/invasion [17], [18], [>>19<<], [20]. In addition, there are a number of other non-hub genes that have been associated with cell migration/invasion such as HAS2 [21] and ACTN1 [22] (Table S1).
n4:mentions: n2:20308542

Subject Item: _:vb20450874
rdf:type: n4:Context
rdf:value: Of the hub genes within the network CCL2, CD44, ANXA1 and ANXA2 have been linked to cell migration/invasion [17], [18], [19], [>>20<<]. In addition, there are a number of other non-hub genes that have been associated with cell migration/invasion such as HAS2 [21] and ACTN1 [22] (Table S1).
n4:mentions: n2:16640645

Subject Item: _:vb20450875
rdf:type: n4:Context
rdf:value: In addition, there are a number of other non-hub genes that have been associated with cell migration/invasion such as HAS2 [>>21<<] and ACTN1 [22] (Table S1).
n4:mentions: n2:16024615

Subject Item: _:vb20450876
rdf:type: n4:Context
rdf:value: In addition, there are a number of other non-hub genes that have been associated with cell migration/invasion such as HAS2 [21] and ACTN1 [>>22<<] (Table S1).
n4:mentions: n2:20037648

Subject Item: _:vb20450877
rdf:type: n4:Context
rdf:value: The proteins evaluated were those previously established to play a role in the invasion and migration of cancer cells: ACTN1, AGT, ANXA2, CCL2, CD44, HAS2 [>>17<<], [18], [20], [22], [23], [24] and denoted by the red circles in Figure 3C.
n4:mentions: n2:21486440

Subject Item: _:vb20450878
rdf:type: n4:Context
rdf:value: The proteins evaluated were those previously established to play a role in the invasion and migration of cancer cells: ACTN1, AGT, ANXA2, CCL2, CD44, HAS2 [17], [>>18<<], [20], [22], [23], [24] and denoted by the red circles in Figure 3C.
n4:mentions: n2:22024282

Subject Item: _:vb20450879
rdf:type: n4:Context
rdf:value: The proteins evaluated were those previously established to play a role in the invasion and migration of cancer cells: ACTN1, AGT, ANXA2, CCL2, CD44, HAS2 [17], [18], [>>20<<], [22], [23], [24] and denoted by the red circles in Figure 3C.
n4:mentions: n2:16640645

Subject Item: _:vb20450880
rdf:type: n4:Context
rdf:value: The proteins evaluated were those previously established to play a role in the invasion and migration of cancer cells: ACTN1, AGT, ANXA2, CCL2, CD44, HAS2 [17], [18], [20], [>>22<<], [23], [24] and denoted by the red circles in Figure 3C.
n4:mentions: n2:20037648

Subject Item: _:vb20450881
rdf:type: n4:Context
rdf:value: The proteins evaluated were those previously established to play a role in the invasion and migration of cancer cells: ACTN1, AGT, ANXA2, CCL2, CD44, HAS2 [17], [18], [20], [22], [>>23<<], [24] and denoted by the red circles in Figure 3C.
n4:mentions: n2:22536420

Subject Item: _:vb20450882
rdf:type: n4:Context
rdf:value: The proteins evaluated were those previously established to play a role in the invasion and migration of cancer cells: ACTN1, AGT, ANXA2, CCL2, CD44, HAS2 [17], [18], [20], [22], [23], [>>24<<] and denoted by the red circles in Figure 3C.
n4:mentions: n2:16125700

Subject Item: _:vb20450883
rdf:type: n4:Context
rdf:value: The complete list of genes includes such invasion/migration associated genes as ADAM10 [>>25<<], HAS2 [21], IL6ST [26], VCAM1 [27] (Table S2).
n4:mentions: n2:19357285

Subject Item: _:vb20450884
rdf:type: n4:Context
rdf:value: The complete list of genes includes such invasion/migration associated genes as ADAM10 [25], HAS2 [>>21<<], IL6ST [26], VCAM1 [27] (Table S2).
n4:mentions: n2:16024615

Subject Item: _:vb20450885
rdf:type: n4:Context
rdf:value: The complete list of genes includes such invasion/migration associated genes as ADAM10 [25], HAS2 [21], IL6ST [>>26<<], VCAM1 [27] (Table S2).
n4:mentions: n2:20361349

Subject Item: _:vb20450886
rdf:type: n4:Context
rdf:value: The complete list of genes includes such invasion/migration associated genes as ADAM10 [25], HAS2 [21], IL6ST [26], VCAM1 [>>27<<] (Table S2).
n4:mentions: n2:19208843

Subject Item: _:vb20450887
rdf:type: n4:Context
rdf:value: In addition, of the 169 genes exclusive to the direct co-culture model 58 could be assigned to an interacting network (Figure 5C; bold genes Table S3) including such genes CTGF [>>28<<], TGFB-2 [29] and CXCL12 [30], which have been associated with invasion/migration.
n4:mentions: n2:18230158

Subject Item: _:vb20450888
rdf:type: n4:Context
rdf:value: In addition, of the 169 genes exclusive to the direct co-culture model 58 could be assigned to an interacting network (Figure 5C; bold genes Table S3) including such genes CTGF [28], TGFB-2 [>>29<<] and CXCL12 [30], which have been associated with invasion/migration.
n4:mentions: n2:11331365

Subject Item: _:vb20450889
rdf:type: n4:Context
rdf:value: In addition, of the 169 genes exclusive to the direct co-culture model 58 could be assigned to an interacting network (Figure 5C; bold genes Table S3) including such genes CTGF [28], TGFB-2 [29] and CXCL12 [>>30<<], which have been associated with invasion/migration.
n4:mentions: n2:16407848

Subject Item: _:vb20450890
rdf:type: n4:Context
rdf:value: Of those molecules a number of have been associated with cell migration/invasion, tissue remodeling and inflammatory response, processes that are likely to influence tumor cell invasion, including MCP-3 (CCL7), osteopontin [>>31<<], TGFB-1 [19], IL-6 [32] and IL-8 [32].
n4:mentions: n2:11126367

Subject Item: _:vb20450891
rdf:type: n4:Context
rdf:value: those molecules a number of have been associated with cell migration/invasion, tissue remodeling and inflammatory response, processes that are likely to influence tumor cell invasion, including MCP-3 (CCL7), osteopontin [31], TGFB-1 [>>19<<], IL-6 [32] and IL-8 [32]. These data suggest that proteins secreted by astrocytes may play a role in mediating CD133+ cell invasion.
n4:mentions: n2:20308542

Subject Item: _:vb20450892
rdf:type: n4:Context
rdf:value: a number of have been associated with cell migration/invasion, tissue remodeling and inflammatory response, processes that are likely to influence tumor cell invasion, including MCP-3 (CCL7), osteopontin [31], TGFB-1 [19], IL-6 [>>32<<] and IL-8 [32]. These data suggest that proteins secreted by astrocytes may play a role in mediating CD133+ cell invasion.
n4:mentions: n2:20953899

Subject Item: _:vb20450893
rdf:type: n4:Context
rdf:value: of have been associated with cell migration/invasion, tissue remodeling and inflammatory response, processes that are likely to influence tumor cell invasion, including MCP-3 (CCL7), osteopontin [31], TGFB-1 [19], IL-6 [32] and IL-8 [>>32<<]. These data suggest that proteins secreted by astrocytes may play a role in mediating CD133+ cell invasion.
n4:mentions: n2:20953899

Subject Item: _:vb20450894
rdf:type: n8:Section
dc:title: discussion
n8:contains: _:vb20450908 _:vb20450909 _:vb20450910 _:vb20450911 _:vb20450904 _:vb20450905 _:vb20450906 _:vb20450907 _:vb20450900 _:vb20450901 _:vb20450902 _:vb20450903 _:vb20450896 _:vb20450897 _:vb20450898 _:vb20450899 _:vb20450895 _:vb20450924 _:vb20450920 _:vb20450921 _:vb20450922 _:vb20450923 _:vb20450916 _:vb20450917 _:vb20450918 _:vb20450919 _:vb20450912 _:vb20450913 _:vb20450914 _:vb20450915

Subject Item: _:vb20450895
rdf:type: n4:Context
rdf:value: To investigate GSC invasion potential, we used two CD133+ cell lines isolated from GBM surgical specimens; as previously reported 13–14 these lines fit the in vitro criteria of tumor stem like cells [>>4<<]. Although additional markers of the GSC phenotype exist [33] and CD133 does not identify all GSCs, the behavior of CD133+ cells used in this study is consistent with the criteria used to GSCs in general [2], [4]. For comparison to a
n4:mentions: n2:14522905

Subject Item: _:vb20450896
rdf:type: n4:Context
rdf:value: Although additional markers of the GSC phenotype exist [>>33<<] and CD133 does not identify all GSCs, the behavior of CD133+ cells used in this study is consistent with the criteria used to GSCs in general [2], [4].
n4:mentions: n2:19427293

Subject Item: _:vb20450897
rdf:type: n4:Context
rdf:value: Although additional markers of the GSC phenotype exist [33] and CD133 does not identify all GSCs, the behavior of CD133+ cells used in this study is consistent with the criteria used to GSCs in general [>>2<<], [4]. For comparison to a non-GSC phenotype, the studies described here used the differentiated progeny of the CD133+ GSCs, which provides an isogenic model system for defining the influence of the stem cell like phenotype on invasion.
n4:mentions: n2:15549107

Subject Item: _:vb20450898
rdf:type: n4:Context
rdf:value: Although additional markers of the GSC phenotype exist [33] and CD133 does not identify all GSCs, the behavior of CD133+ cells used in this study is consistent with the criteria used to GSCs in general [2], [>>4<<]. For comparison to a non-GSC phenotype, the studies described here used the differentiated progeny of the CD133+ GSCs, which provides an isogenic model system for defining the influence of the stem cell like phenotype on invasion.
n4:mentions: n2:14522905

Subject Item: _:vb20450899
rdf:type: n4:Context
rdf:value: Invasion is a complex process involving interactions between tumor cells with the extra-cellular matrix as well as with normal cells [>>34<<]. In an attempt to incorporate such interactions into the in vitro investigation of GBM cell invasion, we used co-cultures of normal human astrocytes with GSCs or their differentiated progeny (non-GSCs).
n4:mentions: n2:22118458

Subject Item: _:vb20450900
rdf:type: n4:Context
rdf:value: The inability of FBS, which is often used as a stimuli for tumor cell invasion [>>16<<], to enhance CD133+ cell invasion in the trans-well assay is also supportive of an astrocyte specific effect.
n4:mentions: n2:15576908

Subject Item: _:vb20450901
rdf:type: n4:Context
rdf:value: Astrocytes serve in multiple functional roles within the CNS under normal conditions as well as in its response to a variety of injuries [>>9<<], [10]. As part of these processes astrocytes influence the behavior of neurons, brain endothelial cells and microglia [9], [10]. More recently, astrocytes have been reported to decrease the chemosensitivity of melanoma and breast tumor
n4:mentions: n2:20012068

Subject Item: _:vb20450902
rdf:type: n4:Context
rdf:value: Astrocytes serve in multiple functional roles within the CNS under normal conditions as well as in its response to a variety of injuries [9], [>>10<<]. As part of these processes astrocytes influence the behavior of neurons, brain endothelial cells and microglia [9], [10]. More recently, astrocytes have been reported to decrease the chemosensitivity of melanoma and breast tumor cell
n4:mentions: n2:12571445

Subject Item: _:vb20450903
rdf:type: n4:Context
rdf:value: As part of these processes astrocytes influence the behavior of neurons, brain endothelial cells and microglia [>>9<<], [10]. More recently, astrocytes have been reported to decrease the chemosensitivity of melanoma and breast tumor cell lines [35], [36]. The data presented herein suggest that an additional attribute of astrocytes is the ability to
n4:mentions: n2:20012068

Subject Item: _:vb20450904
rdf:type: n4:Context
rdf:value: As part of these processes astrocytes influence the behavior of neurons, brain endothelial cells and microglia [9], [>>10<<]. More recently, astrocytes have been reported to decrease the chemosensitivity of melanoma and breast tumor cell lines [35], [36]. The data presented herein suggest that an additional attribute of astrocytes is the ability to enhance GSC
n4:mentions: n2:12571445

Subject Item: _:vb20450905
rdf:type: n4:Context
rdf:value: More recently, astrocytes have been reported to decrease the chemosensitivity of melanoma and breast tumor cell lines [>>35<<], [36]. The data presented herein suggest that an additional attribute of astrocytes is the ability to enhance GSC invasion.
n4:mentions: n2:21390191

Subject Item: _:vb20450906
rdf:type: n4:Context
rdf:value: More recently, astrocytes have been reported to decrease the chemosensitivity of melanoma and breast tumor cell lines [35], [>>36<<]. The data presented herein suggest that an additional attribute of astrocytes is the ability to enhance GSC invasion.
n4:mentions: n2:20824051

Subject Item: _:vb20450907
rdf:type: n4:Context
rdf:value: Astrocytes regulate normal cells within the CNS via a number of cell-cell signaling processes [>>9<<]. The transwell experiments using astrocyte monolayers and conditioned media (Figure 1) indicate that astrocytes can enhance the invasive potential of GSCs through a paracrine based mechanism.
n4:mentions: n2:20012068

Subject Item: _:vb20450908
rdf:type: n4:Context
rdf:value: Whereas it has long been assumed that autocrine factors expressed by GBM cells contribute to their infiltrative character [>>37<<], the data presented here suggest that secreted factors from the normal microenvironment may also contribute to GBM invasion.
n4:mentions: n2:17971532

Subject Item: _:vb20450909
rdf:type: n4:Context
rdf:value: This analysis identified a number of proteins that have not only been associated with tumor cell invasion/migration in general but also that of GBM cells including osteopontin [>>38<<], IL-6 [39], IL-8 [40] MCP-1 [41], VEGF [42], IGFBP-2 [43], GDNF [39], HGF [44], TGFB1 [45] and TGFB2 [39].
n4:mentions: n2:20150368

Subject Item: _:vb20450910
rdf:type: n4:Context
rdf:value: This analysis identified a number of proteins that have not only been associated with tumor cell invasion/migration in general but also that of GBM cells including osteopontin [38], IL-6 [39], IL-8 [>>40<<] MCP-1 [41], VEGF [42], IGFBP-2 [43], GDNF [39], HGF [44], TGFB1 [45] and TGFB2 [39].
n4:mentions: n2:19714445

Subject Item: _:vb20450911
rdf:type: n4:Context
rdf:value: This analysis identified a number of proteins that have not only been associated with tumor cell invasion/migration in general but also that of GBM cells including osteopontin [38], IL-6 [39], IL-8 [40] MCP-1 [>>41<<], VEGF [42], IGFBP-2 [43], GDNF [39], HGF [44], TGFB1 [45] and TGFB2 [39].
n4:mentions: n2:17703277

Subject Item: _:vb20450912
rdf:type: n4:Context
rdf:value: This analysis identified a number of proteins that have not only been associated with tumor cell invasion/migration in general but also that of GBM cells including osteopontin [38], IL-6 [39], IL-8 [40] MCP-1 [41], VEGF [>>42<<], IGFBP-2 [43], GDNF [39], HGF [44], TGFB1 [45] and TGFB2 [39].
n4:mentions: n2:15967572

Subject Item: _:vb20450913
rdf:type: n4:Context
rdf:value: This analysis identified a number of proteins that have not only been associated with tumor cell invasion/migration in general but also that of GBM cells including osteopontin [38], IL-6 [39], IL-8 [40] MCP-1 [41], VEGF [42], IGFBP-2 [>>43<<], GDNF [39], HGF [44], TGFB1 [45] and TGFB2 [39].
n4:mentions: n2:14617774

Subject Item: _:vb20450914
rdf:type: n4:Context
rdf:value: a number of proteins that have not only been associated with tumor cell invasion/migration in general but also that of GBM cells including osteopontin [38], IL-6 [39], IL-8 [40] MCP-1 [41], VEGF [42], IGFBP-2 [43], GDNF [39], HGF [>>44<<], TGFB1 [45] and TGFB2 [39]. Whereas TIMP1 [46] and TIMP2 [46], proteins generally associated with inhibiting cell invasion, were also enriched in the astrocyte conditioned medium, their role in GBM biology may not be straightforward.
n4:mentions: n2:20157762

Subject Item: _:vb20450915
rdf:type: n4:Context
rdf:value: of proteins that have not only been associated with tumor cell invasion/migration in general but also that of GBM cells including osteopontin [38], IL-6 [39], IL-8 [40] MCP-1 [41], VEGF [42], IGFBP-2 [43], GDNF [39], HGF [44], TGFB1 [>>45<<] and TGFB2 [39]. Whereas TIMP1 [46] and TIMP2 [46], proteins generally associated with inhibiting cell invasion, were also enriched in the astrocyte conditioned medium, their role in GBM biology may not be straightforward.
n4:mentions: n2:21156287

Subject Item: _:vb20450916
rdf:type: n4:Context
rdf:value: Whereas TIMP1 [>>46<<] and TIMP2 [46], proteins generally associated with inhibiting cell invasion, were also enriched in the astrocyte conditioned medium, their role in GBM biology may not be straightforward.
n4:mentions: n2:7820957

Subject Item: _:vb20450917
rdf:type: n4:Context
rdf:value: Whereas TIMP1 [46] and TIMP2 [>>46<<], proteins generally associated with inhibiting cell invasion, were also enriched in the astrocyte conditioned medium, their role in GBM biology may not be straightforward.
n4:mentions: n2:7820957

Subject Item: _:vb20450918
rdf:type: n4:Context
rdf:value: That is, increased TIMP1 expression has been correlated with shorter overall survival of GBM patients [>>47<<] and TIMP-2 concentrations have been reported to be greater at the tumor margin [40].
n4:mentions: n2:19430729

Subject Item: _:vb20450919
rdf:type: n4:Context
rdf:value: That is, increased TIMP1 expression has been correlated with shorter overall survival of GBM patients [47] and TIMP-2 concentrations have been reported to be greater at the tumor margin [>>40<<]. Given the number of potentially relevant proteins detected in the astrocyte conditioned media, there are likely to be multiple paracrine factors acting individually and/or in a combinatorial manner to modulate GSC invasion.
n4:mentions: n2:19714445

Subject Item: _:vb20450920
rdf:type: n4:Context
rdf:value: Of those genes unique to direct co-culture 58 could be placed in a network with hub-genes related to invasion and migration such as ICAM1, TGFB2, NRP1, AXL, CXCL12 and CTGF [>>28<<], [29], [48], [49].
n4:mentions: n2:18230158

Subject Item: _:vb20450921
rdf:type: n4:Context
rdf:value: Of those genes unique to direct co-culture 58 could be placed in a network with hub-genes related to invasion and migration such as ICAM1, TGFB2, NRP1, AXL, CXCL12 and CTGF [28], [>>29<<], [48], [49].
n4:mentions: n2:11331365

Subject Item: _:vb20450922
rdf:type: n4:Context
rdf:value: Of those genes unique to direct co-culture 58 could be placed in a network with hub-genes related to invasion and migration such as ICAM1, TGFB2, NRP1, AXL, CXCL12 and CTGF [28], [29], [>>48<<], [49]. These data are consistent with a recent report by Edwards et al. in which orthotopic xenografts initiated from GSCs secrete CTGF, a cytokine they linked to GBM invasion [50]. These results suggest that astrocytes influence the
n4:mentions: n2:16585512

Subject Item: _:vb20450923
rdf:type: n4:Context
rdf:value: Of those genes unique to direct co-culture 58 could be placed in a network with hub-genes related to invasion and migration such as ICAM1, TGFB2, NRP1, AXL, CXCL12 and CTGF [28], [29], [48], [>>49<<]. These data are consistent with a recent report by Edwards et al. in which orthotopic xenografts initiated from GSCs secrete CTGF, a cytokine they linked to GBM invasion [50]. These results suggest that astrocytes influence the expression
n4:mentions: n2:19738068

Subject Item: _:vb20450924
rdf:type: n4:Context
rdf:value: These data are consistent with a recent report by Edwards et al. in which orthotopic xenografts initiated from GSCs secrete CTGF, a cytokine they linked to GBM invasion [>>50<<]. These results suggest that astrocytes influence the expression of a variety of invasion associated genes in GSCs and that the process is mediated by paracrine signaling as well as direct cell contact.
n4:mentions: n2:21771732

Subject Item: _:vb513369546
rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 10
n4:hasRelevantPaperId: n2:15549107

Subject Item: _:vb513369547
rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 10
n4:hasRelevantPaperId: n2:24925914

Subject Item: _:vb513369548
rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 10
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Subject Item: _:vb513369549
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n4:RelevantScore: 8
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Subject Item: _:vb513369550
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n4:RelevantScore: 7
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rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 7
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n4:RelevantScore: 6
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rdf:type: n4:RelevantBibliographicResource
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rdf:type: n4:RelevantBibliographicResource
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rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 6
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rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 6
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rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 6
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rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 6
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rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 6
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rdf:type: n4:RelevantBibliographicResource
n4:RelevantScore: 6
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rdf:type: n4:RelevantBibliographicResource
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rdf:type: n4:RelevantBibliographicResource
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rdf:type: n4:RelevantBibliographicResource
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rdf:type: n4:RelevantBibliographicResource
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n4:hasRelevantPaperId: n2:17971532

Subject Item: _:vb513369570
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