前立腺癌の神経内分泌分化に関わる新規バイオマーカーの同定と診断・治療への応用

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24592391
• Research Institution: Hiroshima University
• Principal Investigator: 松原 昭郎 広島大学, 医歯薬保健学研究院, 教授 (10239064)
• Co-Investigator(Kenkyū-buntansha): 亭島 淳 広島大学, 医歯薬保健学研究院, 講師 (20397962) ; 安井 弥 広島大学, 医歯薬保健学研究院, 教授 (40191118) ; 井上 省吾 広島大学, 大学病院, 助教 (90457177)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 前立腺癌

Outline of Annual Research Achievements

RegIV安定発現LNCaPを用いて細胞増殖能、細胞浸潤能、薬剤感受性への効果を解析、CAST法によって同定されたPRL1およびoligophrenin１においても同様の解析を行い、各分子間における効果の相違を比較した。さらに、前立腺癌細胞の分化異常を促進する分子の一つとしてFGF19に注目、前立腺癌細胞へのFGF19の添加によって上皮間葉移行やアポトーシスの抑制、アンドロゲン除去下での増殖能促進を確認した。また、FGF19の組織内発現は、術後再発の独立した予測因子となること、血清FGF19はGleason scoreが高い症例が多いことを明らかにした。去勢抵抗性前立腺癌症例でのRegIV濃度の測定を昨年度に引き続き行った結果、病勢進行に応じて血清RegIVが高値を示すことを明らかにした。これまでの研究によって、前立腺癌細胞の神経内分泌分化を含む分化異常や上皮間葉移行に関与する分子群が病勢進行や治療効果の予測マーカーとなりうることが示唆された。

Research Products

• [Journal Article] FGF19 promotes progression of prostate cancer. (2015)
  • Author(s): Nagamatsu H, Teishima J, Goto K, Shikuma H, Kitano H, Shoji K, Inoue S, Matsubara A.
  • Journal Title: The Prostate Volume: Apr 8 Pages: Epub
  • DOI: 10.1002/pros.22994
  • Peer Reviewed / Open Access
• [Journal Article] Restoration of fibroblast growth factor receptor 2IIIb enhances the chemosensitivity of human prostate cancer cells. (2014)
  • Author(s): Shoji K, Teishima J, Hayashi T, Ohara S, Mckeehan WL, Matsubara A.
  • Journal Title: Oncology Reports Volume: Jul;32(1) Pages: 65-70
  • DOI: 10.3892/or.2014.3200
  • Peer Reviewed / Open Access
• [Journal Article] Oligophrenin-1 is associated with cell adhesion and migration in prostate cancer. (2014)
  • Author(s): Goto K, Oue N, Hayashi T, Shinmei S, Sakamoto N, Sentani K, Teishima J, Matsubara A, Yasui W.
  • Journal Title: Pathobiology Volume: 81(4) Pages: 190-198
  • DOI: 10.1159/000363345
  • Peer Reviewed / Open Access
• [Journal Article] Identification of PRL1 as a novel diagnostic and therapeutic target for castration-resistant prostate cancer by the Escherichia coli ampicillin secretion trap (CAST) method. (2014)
  • Author(s): Shinmei S, Sentani K, Hayashi T, Sakamoto N, Goto K, Zarni Oo H, Naito Y, Teishima J, Matsubara A, Oue N, Kuniyasu H, Yasui W.
  • Journal Title: Urologic Oncology Volume: Aug;32(6) Pages: 769-778
  • DOI: 10.1016/j.urolonc.2014.03.007
  • Peer Reviewed / Open Access
• [Journal Article] Accumulation of FGF9 in prostate cancer correlates with epithelial-to-mesenchymal transition and induction of VEGF-A expression. (2014)
  • Author(s): Teishima J, Yano S, Shoji K, Hayashi T, Goto K, Kitano H, Oka K, Nagamatsu H, Matsubara A.
  • Journal Title: Anticancer Res Volume: Feb;34(2) Pages: 695-700
  • Peer Reviewed / Open Access
• [Journal Article] Prostate cancer detection by prostate-specific antigen-based screening in the Japanese Hiroshima area shows early stage, low-grade, and low rate of cancer-specific death compared with clinical detection. (2014)
  • Author(s): Teishima J, Maruyama S, Mochizuki H, Oka K, Ikeda K, Goto K, Nagamatsu H, Hieda K, Shoji K, Matsubara A.
  • Journal Title: Canadian Urology Assocciation Journal Volume: May;8(5-6) Pages: E327-332
  • DOI: 10.5489/cuaj.1715
  • Peer Reviewed / Open Access
• [Presentation] 去勢抵抗性前立腺癌におけるregIVの意義 (2014)
  • Author(s): 亭島 淳、正路晃一、山中亮憲、後藤景介、永松弘孝、大原慎也、林 哲太郎、岡 清貴、大上直秀、安井 弥、松原昭郎
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-09-25
• [Presentation] Endocrine FGFs promote progression in prostate cancer. (2014)
  • Author(s): 永松弘孝、亭島 淳、後藤景介、松原昭郎
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-09-25
• [Presentation] Regenerating islet-derived family, member 4 enhances cell proliferation, castration-resistance, and chemoresistance through acceleration of neuroendocrine differentiation in human prostate cancer cells. (2014)
  • Author(s): Jun Teishima, Koichi Shoji, Keisuke Goto, Ryoken Yamaoka, Hiroyuki Shikuma, Hirotaka Nagamatsu, Kiyotaka Oka, Shunsuke Shinmei, Hiroyuki Kitano, Shinya Ohara, Tetsutaro Hayashi, Norihide Oue, Wataru Yasui, Akio Matsubara.
  • Organizer: AUA Annual Meeting 2014
  • Place of Presentation: Orlando
  • Year and Date: 2014-05-19
• [Presentation] Restoration of Fibroblast Growth Factor Receptor 2IIIb Enhances the Chemosensitivity of Human Prostate Cancer Cells. (2014)
  • Author(s): Koichi Shoji, Jun Teishima, Shinya Ohara, Akio Matsubara
  • Organizer: AUA Annual Meeting 2014
  • Place of Presentation: Orlando
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] FGF19 subfamily promotes progression in prostate cancer cells. (2014)
  • Author(s): Hirotaka Nagamatsu, Jun Teishima, Keisuke Goto, Akio Matsubara
  • Organizer: AUA Annual Meeting 2014
  • Place of Presentation: Orlando
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] 前立線癌におけるReg Ⅳの意義. (2014)
  • Author(s): 亭島 淳、永松弘孝、北野弘之、後藤景介、岡 清貴、正路晃一、大上直秀、安井 弥、松原昭郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2014-04-27
• [Presentation] FGF19は前立線癌細胞の増殖を促進する. (2014)
  • Author(s): 永松弘孝、亭島 淳、後藤景介、正路晃一、松原昭郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2014-04-25
• [Presentation] 前立腺癌細胞におけるFGFR2Ⅲbの発現回復は化学療法感受性を増強する. (2014)
  • Author(s): 正路晃一、亭島 淳、大原慎也、松原昭郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2014-04-25
• [Presentation] Regenetrating islet-derived family, member 4 enhances cell proliferation, castration-resistance and chemoresistance through aceleration of neuroendocrine differentiation in human prostate cancer cells. (2014)
  • Author(s): J.Teishima, K.Shoji, K.Goto, R.Yamanaka, H.Shikuma, H.Nagamatsu, S.Shinmei, H.Kitano, S.Ohara, T.hayashi, N.Oue, W.Yasui, A.Matsubara
  • Organizer: 29th Annual EAU Congress
  • Place of Presentation: Stockholm
  • Year and Date: 2014-04-12