Figure 6. Hypothesis of a prostate cancer sphere model system.

Androgen-dependent prostate cancer cells form spheres, with characteristics of prostate cancer stem cells (PCSC), due to epigenomic alterations mediated by an epigenetic modulator PEITC. This step is irreversible. PCSC retain tumorigenic potential and have dual proliferation capabilities allowing self-renewal in the presence and absence of androgen. In the absence of androgen (such as complete androgen blockade therapy/castration), PCSC cells are attenuated in proliferation and initiated differentiation process to neuroendocrine cells (NEC). The androgenome in the NEC cells are reprogramed in the presence of androgen, thereby the NEC cells can de-differentiate to spheres. Since LNCaP cells are epithelial in origin, this step may represent a new phenomenon, epithelial-to-neuroendorine and neuroendocrine-to-epithelial transition.