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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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Principal components analysis of prostate ABCG2+ cells. A: This human prostate PCA space is keyed on the transcriptomes of B, L, S, and E cells. Stem cell transcriptome is represented by that of NCCIT. Putative progenitor cells sorted from the prostate by antibody to ABGC2 (clone 5D3) or in SP are shown. Many 5D3 sorts (red cubes) are found to cluster near E except for that derived from specimen 04-126. This and two SPs are positioned nearer the NCCIT. B: The expression levels of CD133 and CD31 in 04-126, other 5D3 sorts (labeled as "5D3"), endothelial sorts (labeled as CD31+) and SP are indicated by array signal values on a gray scale in the data query display. The histograms below show the same query output. Note the different expression magnitude scales on the y-axis for the two genes.
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Figure 1: Principal components analysis of prostate ABCG2+ cells. A: This human prostate PCA space is keyed on the transcriptomes of B, L, S, and E cells. Stem cell transcriptome is represented by that of NCCIT. Putative progenitor cells sorted from the prostate by antibody to ABGC2 (clone 5D3) or in SP are shown. Many 5D3 sorts (red cubes) are found to cluster near E except for that derived from specimen 04-126. This and two SPs are positioned nearer the NCCIT. B: The expression levels of CD133 and CD31 in 04-126, other 5D3 sorts (labeled as "5D3"), endothelial sorts (labeled as CD31+) and SP are indicated by array signal values on a gray scale in the data query display. The histograms below show the same query output. Note the different expression magnitude scales on the y-axis for the two genes.

Mentions: The prostate SP was isolated due to its slower uptake of Hoechst 33342 due to ABCG2. SP was collected from cells pre-selected by MACS using anti-CD44 since ABCG2+ cells were detected in the CD44+ basal epithelium of the prostate. They constituted a minor population (< 1%) and differed from ABGC2+ endothelial cells of capillaries by expression of the basal marker CD138/SDC1 [18]. In addition to SP, the ABCG2+ cells were sorted from sizable benign tissue specimens using the ABCG2 antibody clone 5D3, and labeled as 5D3 populations [18]. Figure 1A shows a PCA subspace defined by the transcriptomes of basal, luminal, stromal, and endothelial. These four differentiated cell types are distinct in gene expression, and are widely separated in this three dimensional plot. The distance between any two datapoints is a measure of the extent of differential gene expression. Transcriptomes of the SP and 5D3 cells were then projected into this "human prostate" PCA subspace plus the transcriptome of NCCIT used as that of human pluripotent stem cells.


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)

Principal components analysis of prostate ABCG2+ cells. A: This human prostate PCA space is keyed on the transcriptomes of B, L, S, and E cells. Stem cell transcriptome is represented by that of NCCIT. Putative progenitor cells sorted from the prostate by antibody to ABGC2 (clone 5D3) or in SP are shown. Many 5D3 sorts (red cubes) are found to cluster near E except for that derived from specimen 04-126. This and two SPs are positioned nearer the NCCIT. B: The expression levels of CD133 and CD31 in 04-126, other 5D3 sorts (labeled as "5D3"), endothelial sorts (labeled as CD31+) and SP are indicated by array signal values on a gray scale in the data query display. The histograms below show the same query output. Note the different expression magnitude scales on the y-axis for the two genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Principal components analysis of prostate ABCG2+ cells. A: This human prostate PCA space is keyed on the transcriptomes of B, L, S, and E cells. Stem cell transcriptome is represented by that of NCCIT. Putative progenitor cells sorted from the prostate by antibody to ABGC2 (clone 5D3) or in SP are shown. Many 5D3 sorts (red cubes) are found to cluster near E except for that derived from specimen 04-126. This and two SPs are positioned nearer the NCCIT. B: The expression levels of CD133 and CD31 in 04-126, other 5D3 sorts (labeled as "5D3"), endothelial sorts (labeled as CD31+) and SP are indicated by array signal values on a gray scale in the data query display. The histograms below show the same query output. Note the different expression magnitude scales on the y-axis for the two genes.
Mentions: The prostate SP was isolated due to its slower uptake of Hoechst 33342 due to ABCG2. SP was collected from cells pre-selected by MACS using anti-CD44 since ABCG2+ cells were detected in the CD44+ basal epithelium of the prostate. They constituted a minor population (< 1%) and differed from ABGC2+ endothelial cells of capillaries by expression of the basal marker CD138/SDC1 [18]. In addition to SP, the ABCG2+ cells were sorted from sizable benign tissue specimens using the ABCG2 antibody clone 5D3, and labeled as 5D3 populations [18]. Figure 1A shows a PCA subspace defined by the transcriptomes of basal, luminal, stromal, and endothelial. These four differentiated cell types are distinct in gene expression, and are widely separated in this three dimensional plot. The distance between any two datapoints is a measure of the extent of differential gene expression. Transcriptomes of the SP and 5D3 cells were then projected into this "human prostate" PCA subspace plus the transcriptome of NCCIT used as that of human pluripotent stem cells.

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