Neuroendocrine cell differentiation in the CWR22 human prostate cancer xenograft: Association with tumor cell proliferation prior to recurrence

BACKGROUND: Neuroendocrine (NE) cell differentiation is proposed to facilitate prostate cancer (CaP) recurrence following androgen deprivation through secretion by NE cells of growth factors and neuropeptides that support survival and proliferation of CaP cells and vasculature. METHODS: The effect of androgen deprivation on NE differentiation and tumor cell proliferation in the CWR22 model of human CaP was determined by immunohistochemical analysis of the NE cell marker synaptophysin and the cell proliferation marker Ki67. RESULTS: A significant increase in the number of NE cells was observed in CWR22 tumors between 28 and 66 days after castration compared to intact mice, that preceded the increase in tumor cell proliferation that began 70 days after androgen deprivation heralding recurrence. There was a significant positive correlation between the number of tumor-associated NE cells and proliferating CaP cells in tumors from mice after 28-34 days of androgen withdrawal. CONCLUSION: In the CWR22 model, androgen deprivation induces an increase in tumor-associated NE cells prior to increased tumor cell proliferation, with NE cells possibly promoting tumor survival and recurrent disease.