We hypothesize that prostate cancer might arise from tissue specific adult cancer stem cells (ACSC) that reside within the intermediate basal cell population. Studies have shown that following castration in a rat tumor model, the tumors involute and regress to undetectable lesions. However, androgen independent tumors eventually recur suggesting that cancer might arise from residual ACSCs. The hedgehog and WNT/β-catenin canonical pathways are thought to stimulate ACSCs and promote tumor growth. Recently, we have isolated an intermediate basal cell strain from a Gleason score 6 cancer and established an hTERT immortalized cell line, termed IBC-10a. IBC-10a's express 34βE12/p63/Bcl-2/AR/PSA/β-catenin and grow in response to EGF and TGF-β on adherent plates. Putative ACSCs were subsequently isolated from the IBC-10a cultures in two consecutive steps; 1) rapid binding to type I collagen; and 2) growth as spheroids in suspension cultures for ∼28 days. This approach enriched for ACSCs approximately 30 fold. Immunolabeling of spheroids, or “prostospheres” revealed that the prostospheres consisted of ∼10% ACSCs. Characterization of ACSCs (prostospheres) revealed that 50ng/ml SHH stimulated growth of cells in suspension; whereas cyclopamine (10ng/ml) blocked SHH stimulated growth. Furthermore, single cells treated in complete medium supplemented with 10% fetal bovine serum form pseudoglandular structures within collagen I matrices. The isolated cells expressed putative stem cell markers including CD133, ABCG2, ABCA5, and p63 as well as the proto-oncogenes c-myc and c-met. These preliminary results suggest that adult cancer stem cells derived from the intermediate basal cell cultures may be responsible, in part, for the growth of prostate cancer. Supported by and NCI grant CA90397 to MES.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]