Neuroendocrine pathogenesis in adenocarcinoma of the prostate

Background: In the prostate, the importance of sex hormones for its normal development and function is well known. However, it has been proposed that various neuroendocrine (NE) hormones and growth factors may be involved in the pathogenesis of prostatic carcinoma (CaP). Neuroendocrine differentiati on appears to be associated with tumour progression and the androgen-indepe ndent state, for which there is currently no successful therapy. Therefore, we need to improve our understanding of NE cells, their regulatory product s and influence on the prostate gland. Finally, new therapeutic protocols n eed to be developed. Methods: Information is presented on prostatic NE cells and neuroendocrine differentiation (NED) in prostatic carcinoma. Neuroendocrine secretory prod ucts and interactions with epithelial prostate cells are investigated in or der to understand their significance for the pathogenesis of the prostate g land, prognosis and therapy. Results: Recent research suggests that NE-secreted products, such as seroto nin. somatostatin and bombesin, may influence growth, invasiveness, metasta tic processes and angiogenesis in CaP. During recent years, new experimenta l models for NED have been developed to provide evidence that NE products m ay promote proliferation and confer antiapoptotic capabilities on non-neuro endocrine cells in close proximity to NE cells. Cancerous epithelial cells may become more responsive to NE factors by upregulation of receptors for n europeptides, or may induce NE cells to upregulate the secretion and synthe sis of NE factors. In the androgen independent state, neuropeptides and the ir intracellular signals may activate the androgen receptor. Furthermore, a ndrogen ablation may lead to downregulation of neural endopeptidase 24.11 ( a zinc-dependent metalloproteinase) and PSA, which would lead to increased levels of NE products becoming available. These studies confirm that NE cel ls and NED may have a significant impact on prostate cancer, especially in the androgen independent state. Conclusions: Recent developments in molecular biology and pathophysiology o f prostate cancer have increased our understanding of the NE regulatory mec hanisms. Hopefully, this will lead to the development of entirely new thera peutic modalities. For example, somatostatin agonists may suppress angiogen esis and proliferation, and simultaneously promote apoptosis in prostate ca ncer cells. Somatostatin may thus have an important role in tumour biology, and in the future there may be a potential role for somatostatin analogues in the treatment of prostate cancer, but also for serotonin and bombesin r eceptor antagonists. However, a review of the accumulated knowledge in this field suggests that we still need to improve our understanding of NE cells and their regulatory products and influence on the prostate gland, and tha t clinical trials are needed, to test drugs based on neuroendocrine hormone s and their agonists/antagonists.