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n3:pmcid: PMC0
bibo:doi: 10.1038%2Fsj.bjc.6604242
n2:contains: _:vb3178430 _:vb3178416 _:vb3178414

Subject Item: _:vb3178414
rdf:type: n2:Section
dc:title: materials and methods
n2:contains: _:vb3178415

Subject Item: _:vb3178415
rdf:type: n3:Context
rdf:value: Tumour volume was determined by the following formula: V=W2 × L/2 (Carlsson et al, >>1983<<). Once tumours reached greater than 1.5 mm in one dimension, mice were euthanised and tumours were extracted. For flow cytometric analysis, tumours were dissociated with collagenase IV (Sigma) using 200 units ml−1 in DMEM:F12 and
n3:mentions: n4:6833336

Subject Item: _:vb3178416
rdf:type: n2:Section
dc:title: results
n2:contains: _:vb3178427 _:vb3178420 _:vb3178421 _:vb3178422 _:vb3178423 _:vb3178417 _:vb3178418 _:vb3178419 _:vb3178428 _:vb3178429 _:vb3178424 _:vb3178425 _:vb3178426

Subject Item: _:vb3178417
rdf:type: n3:Context
rdf:value: Given the reported similarity between murine breast and prostate stem cells (Lawson et al, >>2007<<) and the recent identification of a CD44+CD24− subpopulation of breast cancer cells that have an increased tumorigenic capacity (Al-Hajj et al, 2003), we sought to identify and characterise CD44+CD24− cells in human prostate cell lines.
n3:mentions: n4:17185413

Subject Item: _:vb3178418
rdf:type: n3:Context
rdf:value: the reported similarity between murine breast and prostate stem cells (Lawson et al, 2007) and the recent identification of a CD44+CD24− subpopulation of breast cancer cells that have an increased tumorigenic capacity (Al-Hajj et al, >>2003<<), we sought to identify and characterise CD44+CD24− cells in human prostate cell lines.
n3:mentions: n4:12629218

Subject Item: _:vb3178419
rdf:type: n3:Context
rdf:value: As Collins et al (>>2005<<) also showed that CD133 is a marker for prostate cancer stem cells, we investigated the CD133 on CD44+CD24− and CD44+CD24−-depleted LNCaP cells.
n3:mentions: n4:16322242

Subject Item: _:vb3178420
rdf:type: n3:Context
rdf:value: The transcription factors Oct-3/4 and BMI-1 are important for embryonic stem cell self-renewal (Niwa, >>2001<<) and long-term proliferative capacity of normal haematopoetic and leukaemic stem cells (Valk-Lingbeek et al, 2004), and are expressed in cancer stem-like cells (Tai et al, 2005; Patrawala et al, 2006).
n3:mentions: n4:11565806

Subject Item: _:vb3178421
rdf:type: n3:Context
rdf:value: The transcription factors Oct-3/4 and BMI-1 are important for embryonic stem cell self-renewal (Niwa, 2001) and long-term proliferative capacity of normal haematopoetic and leukaemic stem cells (Valk-Lingbeek et al, >>2004<<), and are expressed in cancer stem-like cells (Tai et al, 2005; Patrawala et al, 2006).
n3:mentions: n4:15315754

Subject Item: _:vb3178422
rdf:type: n3:Context
rdf:value: are important for embryonic stem cell self-renewal (Niwa, 2001) and long-term proliferative capacity of normal haematopoetic and leukaemic stem cells (Valk-Lingbeek et al, 2004), and are expressed in cancer stem-like cells (Tai et al, >>2005<<; Patrawala et al, 2006).
n3:mentions: n4:15513931

Subject Item: _:vb3178423
rdf:type: n3:Context
rdf:value: stem cell self-renewal (Niwa, 2001) and long-term proliferative capacity of normal haematopoetic and leukaemic stem cells (Valk-Lingbeek et al, 2004), and are expressed in cancer stem-like cells (Tai et al, 2005; Patrawala et al, >>2006<<). An unsupervised analysis, where hierarchical clustering was performed using all genes that were present on 80% of arrays and had a maximum–minimum value of greater than 2 (5713 genes), revealed that CD44+CD24− cells have a gene
n3:mentions: n4:16449977

Subject Item: _:vb3178424
rdf:type: n3:Context
rdf:value: Tumour stem cells should have the property of growing as large unattached sphere in the absence of serum (Dontu et al, >>2003<<; Lee et al, 2006). LNCaP CD44+CD24− cells formed ‘prostatospheres’ when placed in serum-replacement medium, whereas CD44+CD24−-depleted cells grew as an attached monolayer in the same medium (Figure 4A).
n3:mentions: n4:12756227

Subject Item: _:vb3178425
rdf:type: n3:Context
rdf:value: Tumour stem cells should have the property of growing as large unattached sphere in the absence of serum (Dontu et al, 2003; Lee et al, >>2006<<). LNCaP CD44+CD24− cells formed ‘prostatospheres’ when placed in serum-replacement medium, whereas CD44+CD24−-depleted cells grew as an attached monolayer in the same medium (Figure 4A).
n3:mentions: n4:16697959

Subject Item: _:vb3178426
rdf:type: n3:Context
rdf:value: This serum-dependent change in growth pattern was also reported for glioblastoma stem cells (Lee et al, >>2006<<). Furthermore, the serum supplemented CD44+CD24− cells recapitulated the differentiated phenotype of the total LNCaP cells, with only a small percentage of CD44+CD24− cells present, with the majority of the cells being CD44−CD24− (Figure
n3:mentions: n4:16697959

Subject Item: _:vb3178427
rdf:type: n3:Context
rdf:value: The decreased expression of both Oct-3/4 and BMI-1 and the large shift in both phenotype and genotype is consistent with these genes being key regulators in the maintenance of stem cells (Niwa, >>2001<<; Valk-Lingbeek et al, 2004).
n3:mentions: n4:11565806

Subject Item: _:vb3178428
rdf:type: n3:Context
rdf:value: The decreased expression of both Oct-3/4 and BMI-1 and the large shift in both phenotype and genotype is consistent with these genes being key regulators in the maintenance of stem cells (Niwa, 2001; Valk-Lingbeek et al, >>2004<<). Moreover, unsupervised cluster analysis of 4245 genes show a shift in the overall gene expression of the CD44+CD24− cells grown in serum to resemble those of the total LNCaP cell line (Figure 5B). Both of these results are consistent
n3:mentions: n4:15315754

Subject Item: _:vb3178429
rdf:type: n3:Context
rdf:value: Recently, Liu et al (>>2007<<) showed that a gene signature termed the invasiveness gene signature (IGS) can predict overall patient survival in breast, medulloblastoma, lung cancer, and prostate cancer.
n3:mentions: n4:17229949

Subject Item: _:vb3178430
rdf:type: n2:Section
dc:title: discussion
n2:contains: _:vb3178431 _:vb3178436 _:vb3178432 _:vb3178433 _:vb3178434 _:vb3178435

Subject Item: _:vb3178431
rdf:type: n3:Context
rdf:value: Patrawala et al (>>2006<<) recently showed that CD44+ cells derived from prostate cell lines are enriched in tumour progenitor cells, and Collins et al (2005) have demonstrated that CD44+α2β1hiCD133+ cells from patients are highly tumorigenic.
n3:mentions: n4:16449977

Subject Item: _:vb3178432
rdf:type: n3:Context
rdf:value: Patrawala et al (2006) recently showed that CD44+ cells derived from prostate cell lines are enriched in tumour progenitor cells, and Collins et al (>>2005<<) have demonstrated that CD44+α2β1hiCD133+ cells from patients are highly tumorigenic.
n3:mentions: n4:16322242

Subject Item: _:vb3178433
rdf:type: n3:Context
rdf:value: Patrawala et al (>>2006<<) stated that approximately 80% of their CD44+ cells were CD44+α2β1hiCD133+, and they concluded that prostate carcinoma is likely comprised of multiple populations of cells that are able to give rise to tumours with differing efficiencies.
n3:mentions: n4:16449977

Subject Item: _:vb3178434
rdf:type: n3:Context
rdf:value: In agreement with this data, Tang et al (>>2007<<) have recently discussed a hierarchical organisation of prostate stem cells, which places CD44+ cells as an earlier stem cell than the CD44+α2β1hi cells.
n3:mentions: n4:16921491

Subject Item: _:vb3178435
rdf:type: n3:Context
rdf:value: Generally, stem cells are thought to be largely quiescent and to proliferate slowly, eventually giving rise to progenitors that have faster proliferation rates (Tang et al, >>2007<<). Thus, the slow proliferation of CD44+CD24− cells in culture further supports the idea that this subpopulation of cells most likely represents an early progenitor/stem cell.
n3:mentions: n4:16921491

Subject Item: _:vb3178436
rdf:type: n3:Context
rdf:value: This can be highlighted by the fact that breast cancer patients whose tumours have gene expression patterns resembling breast cancer stem cells have a poorer prognosis (Liu et al, >>2007<<). Consequently, the identification of the cancer stem cell and an understanding of the mechanisms driving its self-renewal and differentiation pathways are paramount to targeting and to hopefully eradicating the tumour. To develop
n3:mentions: n4:17229949

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n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:18723679

Subject Item: _:vb370901672
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:19268426

Subject Item: _:vb370901673
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:20713713