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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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Related in: MedlinePlus

Prostate tumor CD44 and CD133 expression. Dataset identities in the histograms are indicated on the x-axis. Red is that of 05-179 CD26+ G3 cancer cells, which shows absent CD44 and CD133 expression.
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Figure 6: Prostate tumor CD44 and CD133 expression. Dataset identities in the histograms are indicated on the x-axis. Red is that of 05-179 CD26+ G3 cancer cells, which shows absent CD44 and CD133 expression.

Mentions: To gauge the frequency of CD44-positive or CD133-positive prostate tumors, a large publicly available prostate cancer dataset [34] was queried. The CD44-CD133- G3 cancer transcriptome was included for comparison (Figure 6). As can be seen, cancer expression of CD133 in these laser-capture microdissected tumor cell specimens was very infrequent. There was more cancer CD44 expression in both primary tumors and metastases. Low frequencies of tumors positive for CD133 (< 1% primary, < 4% bone metastasis) and CD44 (< 10% metastasis) by immunostaining were recently reported by Eaton et al. [35]. CD44 and CD133 expression detected in non-cancer could be due to basal or other cell types as total prostate RNA was used as non-cancer in that analysis [34].


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)

Prostate tumor CD44 and CD133 expression. Dataset identities in the histograms are indicated on the x-axis. Red is that of 05-179 CD26+ G3 cancer cells, which shows absent CD44 and CD133 expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Prostate tumor CD44 and CD133 expression. Dataset identities in the histograms are indicated on the x-axis. Red is that of 05-179 CD26+ G3 cancer cells, which shows absent CD44 and CD133 expression.
Mentions: To gauge the frequency of CD44-positive or CD133-positive prostate tumors, a large publicly available prostate cancer dataset [34] was queried. The CD44-CD133- G3 cancer transcriptome was included for comparison (Figure 6). As can be seen, cancer expression of CD133 in these laser-capture microdissected tumor cell specimens was very infrequent. There was more cancer CD44 expression in both primary tumors and metastases. Low frequencies of tumors positive for CD133 (< 1% primary, < 4% bone metastasis) and CD44 (< 10% metastasis) by immunostaining were recently reported by Eaton et al. [35]. CD44 and CD133 expression detected in non-cancer could be due to basal or other cell types as total prostate RNA was used as non-cancer in that analysis [34].

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