Development of novel therapy for hormone-refractory prostate cancer patients through targeting 5-HT receptor and mast cells

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ER beta is well known to play important roles in the pathogenesis of prostate cancer. Increased expression of 5-HT receptor, especially type 4 (5-HTR4), has been also proposed to be involved in the pathogenesis and peritumoral mast cells have been known to be histopatohologically present. In our immunohistochemical analysis (n=112), 5-HTR4 immunoreactivity was detected in 34% cases, and its immunoreactivity was significantly correlated with that of ER beta. Peritumoral mast cells, a potential site of serotonin production, were abundant within the tissues. 24h incubation of LNCaP cells with 5-HTR4 agonist increased the expression level of ER beta mRNA, while inhibited migration of cancer cells compared to controls.These findings indicated that 5-HTR4 may be involved in the pathogenesis of human prostate cancer cells possibly through 5-HT secreted by peritumoral mast cells.