Premium
Neuroendocrine cell differentiation in the CWR22 human prostate cancer xenograft: Association with tumor cell proliferation prior to recurrence
Author(s) -
Huss Wendy J.,
Gregory Christopher W.,
Smith Gary J.
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20032
Subject(s) - synaptophysin , cell growth , prostate cancer , androgen deprivation therapy , androgen , medicine , endocrinology , neuroendocrine differentiation , proliferation marker , cancer research , prostate , biology , cell cycle , immunohistochemistry , cell , cancer , hormone , genetics
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. © 2004 Wiley‐Liss, Inc.