Abstract
Abstract Cancer Stem cells (CSCs) or tumor initiating cells (TICs) have recently been identified in solid tumors; however, the role of CSCs/TICs in metastasis remains poorly understood. In this study, we developed a pre-clinical model to study stem-like cells in prostate cancer metastasis. CS-5 and CS-10 cells were derived by growing parental LNCaP cells in androgen-depleted media for five and ten generations. The growth rate of CS-10 cells was similar to parenteral LNCaP cells while CS-5 cell growth was diminished. Interestingly, CS10 cells were the sole cells observed with CD44 expression, which also had the highest α2β1 expression. In addition, none of the cell lines expressed CD133. In contrast to parenteral LNCaP cells, CD44+ CS-10 cells displayed an increase in 5 min collagen-I attachment, cell migration, invasion, colony formation and sphere formation in an anchorage-independent environment, all attributes of TICs. Additional evidence for “stemness” was that CS-10 cells were capable of self-renewal in the secondary and tertiary spheroid assays. CS-10 cells expressed neuroendocrine and EMT markers and demonstrated resistance to anti-androgen drugs and most chemotherapeutic drugs compared to parenteral LNCaP cells. In summary, the novel findings presented here provide evidence that castrate resistance may result in selection of CD44+/ α2β1+/CD24low/CD133 cells, which possesses stem cell properties. This cell line may serve as a model for evaluation of new targeted treatments in prostate CSCs. Citation Format: Lisa Y. Wu, Nitu Bansal, Tiancheng Liu, Clifford E. Berkman, Joseph R. Bertino. Androgen resistance in prostate cancer is associated with an enrichment of stem-like cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 214. doi:10.1158/1538-7445.AM2014-214
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