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

众所周知，ERβ在前列腺癌的发病机制中起着重要作用。5-羟色胺受体，特别是4型(5-HTR4)的表达增加也被认为参与了肿瘤的发病机制，并且已知瘤周肥大细胞存在于组织病理学中。在我们的免疫组织化学分析中(n=112)，34%的病例检测到5-HTR4的免疫反应，并且其免疫反应与ERβ的表达显著相关。瘤周肥大细胞是产生5-羟色胺的潜在部位，在组织中含量丰富。与对照组相比，LNCaP细胞与5-HTR4激动剂孵育24小时后，ERβmRNA表达水平升高，癌细胞迁移受到抑制，提示5-HTR4可能通过瘤周肥大细胞分泌5-羟色胺参与前列腺癌的发病过程。

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.