Lineage relationship of prostate cancer cell types based on gene expression

Abstract

BackgroundProstate 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.MethodsTranscriptomes 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.ResultsBased 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.ConclusionsNon-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.

Loss of Let-7 MicroRNA Upregulates IL-6 in Bone Marrow-Derived Mesenchymal Stem Cells Triggering a Reactive Stromal Response to Prostate Cancer

“…Intercelluar adhesion relies heavily on the association between cell adhesion molecules expressed on the cell surfaces. The difference in the expression profiles of cell adhesion molecules among LNCaP, C4-2 and PC3 cells [39] may be the major causes of varied aggregate size seen in the present study. It has been demonstrated that cell shape, which is determined by the internal organization of the cytoskeleton as well as by interactions between adjacent cells and the surrounding matrix, has a strong influence on the switch in lineage commitment of MSCs.…”

Prostate cancer cell phenotypes based on AGR2 and CD10 expression

“…LuCaP 35 is similar to LNCaP in gene expression; both were established from positive lymph nodes. 20 LuCaP 49, characterized by minimal AGR2 and CD10 expression, is representative of small cell carcinoma. 21 Among them, these phenotypes were found – CD10 − AGR2 + G3 cancer, CL1, PC3; CD10 high AGR2 low LuCaP 35; CD10 − AGR2 low G4 cancer; CD10 + AGR2 − LNCaP, C4-2; CD10 − AGR2 − DU145, LuCaP 49.…”

“…Similarly, although G3 cancer and CL1 shared a common phenotype in AGR2 and CD10, their overall gene expression is very different. 20 …”

Bladder expression of CD cell surface antigens and cell-type-specific transcriptomes

“…Basal cells have recently been reported to be the cell type of origin for prostate cancer (Goldstein et al 2010). However, none of the cancer cell types, including some considered to represent the so-called cancer stem cell type, profiled by array analysis shows much basal cell gene expression (Pascal et al 2011b). Like prostate cancer, the bladder cancer profiled here (07-008CB) is luminal in expression signature, by cytokeratins KRT18 + /KRT5 − .…”