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 differentiation appears to be associated with tumour progression and the androgen-independent state, for which there is currently no successful therapy. Therefore, we need to improve our understanding of NE cells, their regulatory products and influence on the prostate gland. Finally, new therapeutic protocols need to be developed.


METHODS
Information is presented on prostatic NE cells and neuroendocrine differentiation (NED) in prostatic carcinoma. Neuroendocrine secretory products and interactions with epithelial prostate cells are investigated in order to understand their significance for the pathogenesis of the prostate gland, prognosis and therapy.


RESULTS
Recent research suggests that NE-secreted products. such as serotonin, somatostatin and bombesin, may influence growth, invasiveness, metastatic processes and angiogenesis in CaP. During recent years. new experimental models for NED have been developed to provide evidence that NE products may promote proliferation and confer antiapoptotic capabilities on non-neuroendocrine cells in close proximity to NE cells. Cancerous epithelial cells may become more responsive to NE factors by upregulation of receptors for neuropeptides, or may induce NE cells to upregulate the secretion and synthesis of NE factors. In the androgen independent state, neuropeptides and their intracellular signals may activate the androgen receptor. Furthermore, androgen 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 cells and NED may have a significant impact on prostate cancer, especially in the androgen independent state.


CONCLUSIONS
Recent developments in molecular biology and pathophysiology of prostate cancer have increased our understanding of the NE regulatory mechanisms. Hopefully, this will lead to the development of entirely new therapeutic modalities. For example, somatostatin agonists may suppress angiogenesis and proliferation, and simultaneously promote apoptosis in prostate cancer 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 receptor 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 that clinical trials are needed, to test drugs based on neuroendocrine hormones and their agonists/antagonists.
Hansson
J
J
Department of Urology, University Hospitals of Lund, University of Lund, Sweden.
Abrahamsson
P A
PA
D000230:Adenocarcinoma / Q000503:physiopathology*; D000728:Androgens / Q000494:pharmacology; D002454:Cell Differentiation; D018450:Disease Progression; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic; D009479:Neuropeptides / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*
D000728:Androgens; D009479:Neuropeptides