Lineage relationship of prostate cancer cell types based on gene expression

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.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.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.Tumor heterogeneity is a major hurdle in effective treatment of the disease. This heterogeneity could be due to multiple cancer cell types with distinct gene expression. How do these cell types arise? The cancer stem cell hypothesis states that tumors are propagated by cancer cells with stem-cell characteristics, and that tumor heterogeneity results from differentiation of these stem-like cells. Tumors from several tissue types have been found to contain specific populations of tumorigenic and non-tumorigenic cells. Breast tumor formation can be initiated by a small number of tumorigenic cells characterized as CD44+CD24lo/-, while non-tumorigenic cells are CD44-CD24+. The latter could be generated from the former during tumor gro