Functional Implications of Neuroendocrine Differentiated Cells in Prostate Cancer

This thesis focuses on NE differentiation in prostate cancer, especially in prostate cancer models. We studied the effects of androgen depletion on the NE differentiated status of in vivo and in vitro prostatic tumor models. Knowledge concerning the function of NE cells in the normal human prostate and in prostate cancer is limited. A number of groups have studied NE differentiation in different epithelial systems. NE cells were found to be present in most prostatic adenocarcinomas (DiSant'Agnese, 1994). There is accumulating evidence that NE cells and tumors with NE cells are related to the androgen independent and poorly differentiated types of prostate cancer. There are indications that at least some secretion products of prostatic NE cells, like GRP and 5-HT, affect both prostate cancer growth and possibly also tumor differentiation. However, the growth modulating effects of neuropeptides and their relation to circulating androgen levels and androgen sensitivity of prostate cancer need to be further assessed. Studies directed towards identifying the role of NE cells in hormonally treated prostate cancer may contribute to the understanding of the transition of androgen dependent to androgen independent prostate cancer. There are still unanswered questions that need to be answered: How is the process of neuroendocrine differentiation regulated and can this process be influenced? Are the NE cells necessary for the regulation of growth and differentiation of the prostate or do they play a role in the maintenance of prostatic homeostasis? Can these cells induce (androgen independent) growth of surrounding cells, for instance by ligand independent activation of the androgen receptor (AR) through neuropeptides secreted by NE cells?