Abstract A68: Involvement of serotonin receptor 4 (5-HTR4) in estrogen receptor beta (ER beta) expression and invasion of peritumoral mast cells in human prostate cancer tissue

Abstract

Abstract Background: Androgens have been proposed to play pivotal roles in the development of human prostate cancer, and blockades of their actions have been also established as effective treatment of the patients. However, development of hormone-refractory prostate cancer (HRPC) is generally imminent and has emerged as one of the most critical clinical problems in the long-term management of the patients with prostate cancer. We previously postulated the significance of in situ androgen and estrogen production in human prostate cancer tissues in HRPC achievement via androgen receptor (AR) and estrogen receptor beta (ER beta). The role for neuroendocrine differentiation (NED) in prostate cancer tissues has also been considered important in the development of high grade/stage. Carcinoma cells with NED produce and secrete serotonin (5-HT), and increased expression of 5-HT receptor, especially type 4 (5-HTR4), has been proposed to be involved in autocrine/paracrine loops to sustain growth of HRPC. While, mast cell recruitment around the tumor cells has been proposed to be involved during the formation of HRPC, which may also contribute to stimulating effects on angiogenesis in local environment. Mast cells are also known to produce and secret 5-HT. Therefore, our hypothesis is that 5-HT secreted by both carcinoma and mast cells may be involved in autocrine/paracrine environment to develop HRPC via 5-HTR4. In addition, 5-HTR4 expression level is possibly associated with local microenvironment regulated by androgen and estrogen. Experimental design: We evaluated the expression levels of 5-HTR4 as well as the number of peritumoral mast cells and 5-HT positive carcinoma cells in human prostate cancer (n=112) using immunohistochemistry and correlated the findings with clinicopathological features of the patients and the expression levels of AR and ER beta. Results: 5-HTR4 immunoreactivity was detected in 38 cases of prostate cancer (34%). In the cases positive for 5-HTR4, the number of peritumoral mast cells tended to be higher than those negative for the receptor, while 5-HT positive cells were sparsely detectable in all the cases. In addition, 5-HTR4 immunoreactivity was significantly correlated with that of ER beta (P<0.05). The status of 5-HTR4 immunoreactivity was not significantly correlated with clinicopathological parameters of the cases examined including patient age, concentration of serum PSA levels, Gleason score, pT stage, lymph node states, or AR level. Conclusion: These data all suggest that 5-HTR4 plays a functional role in human prostate cancer via 5-HT secreted by both carcimoma and peritumoral mast cells. In addition, estrogens may possibly regulate the roles of 5-HTR4 via ER beta as previously reported in the other tissue, and their association may influence the development of HRPC. Note: This abstract was not presented at the conference because the presenter was unable to attend. Citation Format: Yasuhiro Nakamura, Takashi Maekawa, Kazue Ise, Shigeto Ishidoya, Yoichi Arai, Hironobu Sasano. Involvement of serotonin receptor 4 (5-HTR4) in estrogen receptor beta (ER beta) expression and invasion of peritumoral mast cells in human prostate cancer tissue [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A68.