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Lineage relationship of prostate cancer cell types based on gene expression.

Pascal LE, Vêncio RZ, Vessella RL, Ware CB, Vêncio EF, Denyer G, Liu AY - BMC Med Genomics (2011)

Bottom Line: The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types.However, none showed expression of stem cell genes known to maintain stemness.Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology University of Washington, Seattle, WA 98195, USA.

ABSTRACT

Background: Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells.

Methods: Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology) and pattern 4 (aglandular) sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype) and LuCaP 49 (neuroendocrine/small cell carcinoma) grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts.

Results: Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like) grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness.

Conclusions: Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

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Gene expression comparison of ABCG2+ cells and stem cells. A: Differential expression of selected genes between 5D3 (04-126), SP and ES (H1) and EC (NCCIT) cells as obtained from dataset query is shown. B: PCA plot of H1 and NCCIT shows the close relatedness between these two cell types.
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Figure 2: Gene expression comparison of ABCG2+ cells and stem cells. A: Differential expression of selected genes between 5D3 (04-126), SP and ES (H1) and EC (NCCIT) cells as obtained from dataset query is shown. B: PCA plot of H1 and NCCIT shows the close relatedness between these two cell types.

Mentions: Dataset comparison was carried out between SP, 5D3 (04-126) and EC, ES. The expression pattern of several genes in these populations is shown in Figure 2A. First, note the similarity between EC and ES cells in the expression levels of stem cell markers SOX2, LIN28, NANOG, POU5F1/LOC642559, TDGF1 (CRIPTO) and PROM1 (CD133). In addition, stem cell marker could also be considered for CD9 [28] and THY1 (CD90) [29]. Figure 2B shows the proximity of ES (H1) and EC (NCCIT) in gene expression by PCA. For POU5F1 (OCT4), two Affymetrix probesets (235842_at, 238997_at) produced no signal while two others, LOC642559 (210265_x_at) and LOC645682 (210905_x_at), gave strong signals. Both SP and 5D3 cells showed low expression levels of these stem cell genes. NCCIT was negative for ABCG2 expression [18], so were the ES cells in contrast to SP and 5D3, which were obtained based on ABCG2 expression. Despite these differences, the overall gene expression of the 5D3 and SP populations was more similar to that of stem cells than to any of the differentiated cell types (i.e., L, S, B, E) as indicated by PCA. There were 13,413 genes with signal intensity values > 100 expressed in common by all three (> 80%); 15,899 between ES and EC; 14,404 between ES and 5D3; 14,913 between EC and 5D3. The common pool for SP and ES/EC was 13,122, and 16,300 between 5D3 and SP. Accordingly, the PCA display could be viewed as a cell differentiation space in which the undifferentiated stem/progenitor cells appeared to occupy a more interior position and the differentiated cell types were positioned towards the periphery. Relatedness between cell types was indicated by the separation of the datapoints. Thus, the gene expression difference between the epithelial cell types (luminal and basal) was almost as large as that between epithelial and stromal cells. These three prostate cell types have their individual complement of CD molecules [30].


Lineage relationship of prostate cancer cell types based on gene expression.

Pascal LE, Vêncio RZ, Vessella RL, Ware CB, Vêncio EF, Denyer G, Liu AY - BMC Med Genomics (2011)

Gene expression comparison of ABCG2+ cells and stem cells. A: Differential expression of selected genes between 5D3 (04-126), SP and ES (H1) and EC (NCCIT) cells as obtained from dataset query is shown. B: PCA plot of H1 and NCCIT shows the close relatedness between these two cell types.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113924&req=5

Figure 2: Gene expression comparison of ABCG2+ cells and stem cells. A: Differential expression of selected genes between 5D3 (04-126), SP and ES (H1) and EC (NCCIT) cells as obtained from dataset query is shown. B: PCA plot of H1 and NCCIT shows the close relatedness between these two cell types.
Mentions: Dataset comparison was carried out between SP, 5D3 (04-126) and EC, ES. The expression pattern of several genes in these populations is shown in Figure 2A. First, note the similarity between EC and ES cells in the expression levels of stem cell markers SOX2, LIN28, NANOG, POU5F1/LOC642559, TDGF1 (CRIPTO) and PROM1 (CD133). In addition, stem cell marker could also be considered for CD9 [28] and THY1 (CD90) [29]. Figure 2B shows the proximity of ES (H1) and EC (NCCIT) in gene expression by PCA. For POU5F1 (OCT4), two Affymetrix probesets (235842_at, 238997_at) produced no signal while two others, LOC642559 (210265_x_at) and LOC645682 (210905_x_at), gave strong signals. Both SP and 5D3 cells showed low expression levels of these stem cell genes. NCCIT was negative for ABCG2 expression [18], so were the ES cells in contrast to SP and 5D3, which were obtained based on ABCG2 expression. Despite these differences, the overall gene expression of the 5D3 and SP populations was more similar to that of stem cells than to any of the differentiated cell types (i.e., L, S, B, E) as indicated by PCA. There were 13,413 genes with signal intensity values > 100 expressed in common by all three (> 80%); 15,899 between ES and EC; 14,404 between ES and 5D3; 14,913 between EC and 5D3. The common pool for SP and ES/EC was 13,122, and 16,300 between 5D3 and SP. Accordingly, the PCA display could be viewed as a cell differentiation space in which the undifferentiated stem/progenitor cells appeared to occupy a more interior position and the differentiated cell types were positioned towards the periphery. Relatedness between cell types was indicated by the separation of the datapoints. Thus, the gene expression difference between the epithelial cell types (luminal and basal) was almost as large as that between epithelial and stromal cells. These three prostate cell types have their individual complement of CD molecules [30].

Bottom Line: The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types.However, none showed expression of stem cell genes known to maintain stemness.Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology University of Washington, Seattle, WA 98195, USA.

ABSTRACT

Background: Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells.

Methods: Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology) and pattern 4 (aglandular) sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype) and LuCaP 49 (neuroendocrine/small cell carcinoma) grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts.

Results: Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like) grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness.

Conclusions: Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

Show MeSH
Related in: MedlinePlus