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

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tohoku University
• Principal Investigator: NAKAMURA Yasuhiro 東北大学, 医学(系)研究科(研究院), 准教授 (80396499)
• Co-Investigator(Renkei-kenkyūsha): SASANO Hironobu 東北大学, 大学院医学系研究科, 教授 (50187142)
• Project Period (FY): 2011 – 2013
• Keywords: 前立腺癌 / セロトニン受容体 / エストロゲン受容体 / 肥満細胞

Research Abstract

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.

Research Products

• [Presentation] ヒト前立腺癌組織での5-HTR4によるエストロゲン受容体β(ERβ)の発現調節 (2014)
  • Author(s): 中村保宏, 伊勢和恵, フェリゾラサウロ, 齊藤涼子, 佐藤聡子, 前川尚志, 深谷佐智子, 佐藤直実, 勝罵浩紀, 柴原裕紀子, 板倉裕子, 谷内真司, 笠島敦子, 藤島史喜, 渡辺みか, 荒井陽一, 笹野公伸
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-25
• [Presentation] Serotonin receptor 4 (5-HTR4) regulates expression of ER beta (ER(3) and cell growth in human prostate cancer (2013)
  • Author(s): Yasuhiro Nakamura, Kazue Ise, Saulo JA Felizola, Keely M McNamara, Hironobu Sasano
  • Organizer: ENDO 2013
  • Place of Presentation: 米国, サンフランシスコ
  • Year and Date: 2013-06-15
• [Presentation] Involvement of serotonin receptor 4 (5-HTR4) in ER beta expression and cancer development through peritumoral mast cells in human prostate cancer tissue (2013)
  • Author(s): Yasuhiro Nakamura, Kazue Ise, Keely McNamara, Hironobu Sasano
  • Organizer: Ninth AACR-Jananese Cancer Association Joint Conference
  • Place of Presentation: 米国, マウイ
  • Year and Date: 2013-02-25
• [Presentation] Involvement of serotonin receptor 4 (5-HTR4) in ER beta expression and invasion of peritumoral mast cells in human prostate cancer tissue (2012)
  • Author(s): Yasuhiro Nakamura, Takashi Maekawa, Kazue Ise, Shigeto Ishidoya, Yoichi Arai, Hironobu Sasano
  • Organizer: Advances in Prostate Cancer Research
  • Place of Presentation: 米国, オーランド
  • Year and Date: 2012-02-07