Autocrine expression of neurotrophins and their receptors in prostate cancer

Previously, it has been demonstrated that the neurotrophins and their recep tors are present in human prostate tissue, but neither their functional rol e nor localization is clearly understood. We studied the expression of neur otrophins and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer specimens were obtained from patients undergoing radical p rostatectomy, of whom 25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The specimens were analyzed immunohistochemically for neur otrophins (nerve growth factor, brain derived neurotrophic factor, neurotro phin 3, neurotrophin 4/5) and their receptors (TrkA, TrkB, TrkC, p75NTR). I mmunohistochemical studies revealed that both benign and malignant prostate gland epithelial cells expressed the neurotrophins and their receptors to various degrees, but no obvious immunopositive reaction was observed in str omal cells. In benign epithelial cells, the neurotrophins were localized to secretory cells and the receptors were localized to basal cells. The neuro trophins, TrkA and TrkC were expressed to a similar extent in prostate canc er specimens obtained from patients both with and without NHT. In contrast, the expression of TrkB was downregulated and the expression of p75NTR was up-regulated in prostate cancer after hormonal therapy. These findings sugg est that neurotrophins are secreted by prostate cancer cells in an autocrin e fashion. Neurotrophins may be involved, through their receptors, in the e scape mechanism from cell death after androgen depletion found in prostate cancer.