Lineage relationship of prostate cancer cell types based on gene expression
1 Department of Urology University of Washington, Seattle, WA 98195, USA
2 Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA
3 University of Pittsburgh Medical Center, Department of Urology, Pittsburgh, PA 15232, USA
4 Genetics Department, University of São Paulo's Medical School at Ribeirão Preto, Brazil
5 Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA
6 Department of Pathology, Federal University of Goias, Goiania, Brazil
7 Department of Biochemistry, The University of Sydney, Sydney, Australia
BMC Medical Genomics 2011, 4:46 doi:10.1186/1755-8794-4-46Published: 23 May 2011
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.
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.