A new therapeutic strategy for targeting carcinoma-associated fibroblast-derived KGF in castration resistant prostate cancer

• Project/Area Number: 21791499
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Mie University
• Principal Investigator: ISHII Kenichiro Mie University, 大学院・地域イノベーション学研究科, 研究員 (90397513)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 再燃前立腺癌 / 癌間質 / KGF / 線維芽細胞 / 筋線維芽細胞 / TGFβ / 前立腺癌 / 癌間質モデル / KGF/FGF-7 / 筋線維芽胞 / α_1ブロッカー / 細胞周期阻害 / IL-6 / FGF-7 / 代替細胞 / 平滑筋細胞

Research Abstract

Our results showed that TGFβ-induced myofibroblastic differentiation in PrSC reduced the expression of KGF mRNA. Thus, we suggest that type of stromal cells surrounding cancer cells may be important in the progression of castration resistant prostate cancer.

Research Products

• [Journal Article] Naftopidil, a subtype selective alpha1-adrenoceptor antagonist, suppresses human prostate tumor growth by altering interactions between tumor cells and stroma. (2011)
  • Author(s): Hori Y, Ishii K, Kanda H, Iwamoto Y, Nishikawa K, Soga N, Kise H, Arima K, Sugimura Y.
  • Journal Title: Cancer Prevention Research 4 Pages: 87-96
  • Peer Reviewed
• [Journal Article] Naftopidil, a subtype selective alphal-adrenoceptor antagonist, suppresses human prostate tumor growth by altering interactions between tumor cells and stroma. (2011)
  • Author(s): Hori Y, Ishii K, Kanda H, Iwamoto Y, Nishikawa K, Soga N, Kise H, Arima K, Sugimura Y.
  • Journal Title: Cancer Prevention Research Volume: 4 Pages: 87-96
  • Peer Reviewed
• [Journal Article] Effect of transforming growth factor α overexpression on urogenital organ development in mouse. (2010)
  • Author(s): Yoshio Y, Ishii K, Arase S, Hori Y, Nishikawa K, Soga N, Kise H, Arima K, Sugimura Y.
  • Journal Title: Differentiation 80 Pages: 82-88
  • Peer Reviewed
• [Journal Article] Structural changes in alpha1-adrenoceptor antagonist-treated human prostatic stroma. (2010)
  • Author(s): Imamura T, Ishii K, Kanda H, Arase S, Yoshio Y, Hori Y, Soga N, Kise H, Arima K, Sugimura Y.
  • Journal Title: Clinical and Experimental Medicine 10(equal contributor) Pages: 99-106
  • Peer Reviewed
• [Journal Article] Endodermal origin of bladder trigone inferred from mesenchymal-epithelial interactions. (2010)
  • Author(s): Tanaka ST, Ishii K, DeMarco RT, Pope JC, Brock JW, Hayward SW.
  • Journal Title: Journal of Urology 183 Pages: 386-391
  • Peer Reviewed
• [Journal Article] Effect of transforming growth factor α overexpression on urogenital organ development in mouse. (2010)
  • Author(s): Yoshio Y, Ishii K, Arase S, Hori Y, Nishikawa K, Soga N, Kise H, Arima K, Sugimura Y.
  • Journal Title: Differentiation Volume: 80 Pages: 82-88
  • Peer Reviewed
• [Journal Article] Adult urothelial transdifferentiation to prostate epithelia is mediated by paracrine TGF-β signaling. (2009)
  • Author(s): Li X, Wang Y, Sharif-Afshar AR, Uwamariya C, Yi A, Ishii K, Hayward SW, Matusik RJ, Bhowmick NA.
  • Journal Title: Differentiation 77 Pages: 95-102
  • Peer Reviewed
• [Journal Article] Evidence that androgen-independent stromal growth factor signals promote androgen-insensitive prostate cancer cell growth in vivo. (2009)
  • Author(s): Ishii K, Imamura T, Iguchi K, Arase S, Yoshio Y, Arima K, Hirano K, Sugimura Y.
  • Journal Title: Endocrine-Related Cancer 16 Pages: 415-428
  • Peer Reviewed
• [Journal Article] Evidence that androgen-independent stromal growth factor signals promote androgen-insensitive prostate cancer cell growth in vivo. (2009)
  • Author(s): Ishii K, Imamura T, Iguchi K, Arase S, Yoshio Y, Arima K, Hirano K, Sugimura Y
  • Journal Title: Endocrine-Related Cancer 16 Pages: 415-428
  • Peer Reviewed
• [Journal Article] Endocrine disrupter bisphenol A increases in situ estrogen production in mouse urogenital sinus.
  • Author(s): Arase S, Ishii K, Igarashi K, Aisaki K, Yoshio Y, Matsushima A, Shimohigashi Y, Arima K, Kanno J, Sugimura Y.
  • Journal Title: Biology of Reproduction in press(equal contributor)
  • Peer Reviewed
• [Journal Article] Endocrine disrupter bisphenol A increases in situ estrogen production in mouse urogenital sinus.
  • Author(s): Arase S, Ishii K, Igarashi K, Aisaki K, Yoshio Y, Matsushima A, Shimohigashi Y, Arima K, Kanno J, Sugimura Y.
  • Journal Title: Biology of Reproduction Volume: (in press)
  • Peer Reviewed
• [Journal Article] Structural changes in alphal-adrenoceptor antagonist-treated human prostatic stroma.
  • Author(s): Imamura T, Ishii K, Kanda H, Arase S, Yoshio Y Hori Y, Soga N, Kise H, Arima K, Sugimura Y.
  • Journal Title: Clinical and Experimental Medicine (in press)
  • Peer Reviewed
• [Presentation] ヒト前立腺癌間質モデルの作製と発生メカニズムの解析 (2011)
  • Author(s): 石井健一朗、溝上敦、西川晃平、岩本陽一、加藤学、曽我倫久人、木瀬英明、有馬公伸、並木幹夫、杉村芳樹
  • Organizer: 第20回泌尿器科分子・細胞研究会
  • Place of Presentation: 津市
• [Presentation] 前立腺癌組織における新規神経内分泌物質Manserin発現の検討 (2011)
  • Author(s): 西川晃平、曽我倫久人、加藤学、岩本陽一、石井健一朗、山田泰司、有馬公伸、杉村芳樹
  • Organizer: 第20回泌尿器科分子・細胞研究会
  • Place of Presentation: 津市
• [Presentation] 胎生期ビスフェノールA曝露による前立腺の異常増殖機構 (2010)
  • Author(s): 石井健一朗、荒瀬栄樹、吉尾裕子、杉村芳樹(指定演題)
  • Organizer: 第26回前立腺シンポジウム
  • Place of Presentation: 品川
• [Presentation] Heterogeneity of carcinoma-associated fibroblast-like differentiation in normal human prostatic fibroblasts (2010)
  • Author(s): 石井健一朗、堀靖英、溝上敦、山田泰司、有馬公伸、並木幹夫、杉村芳樹
  • Organizer: 第69回日本癌学会総会学術総会
  • Place of Presentation: 大阪市
• [Presentation] Experimental approach targeting tumor-stromal interactions in prostate cancer microenvironment (2010)
  • Author(s): 杉村芳樹、石井健一朗(指定演題)
  • Organizer: 第69回日本癌学会総会学術総会
  • Place of Presentation: 大阪市
• [Presentation] Phenylpiperazine derivatives induce G1 cell cycle arrest in human prostate cancer cells and stromal cells (2010)
  • Author(s): 堀靖英、石井健一朗、山田泰司、有馬公伸、杉村芳樹
  • Organizer: 第69回日本癌学会総会学術総会
  • Place of Presentation: 大阪市
• [Presentation] Characterization of androgen-low sensitive LNCaP subline, LNCaP-E9 cells (2010)
  • Author(s): Kazuhiro Iguchi, Kazuhiro Fukami, Kenichiro Ishii, Shigeyuki Usui, Yoshiki Sugimura, Kazuyuki Hirano
  • Organizer: 38^<th> Congress of the International Society of Oncology and Biomarkers (ISOBM)
  • Place of Presentation: Munchen
• [Presentation] 胎生期ビスフェノールA曝露による前立腺の異常増殖機構 (2010)
  • Author(s): 石井健一朗(指定演題)
  • Organizer: 第3回前立腺生物学シンポジウム
  • Place of Presentation: 鳥羽市
• [Presentation] Biological effects of fetal exposure to bisphenol A on urogenital sinus (2010)
  • Author(s): Kenichiro Ishii, Shigeki Arase, Yuko Yoshio, Katsuhide Igarashi, Kenichi Aisaki, Yasuhide Hori, Kohei Nishikawa, Norihito Soga, Hideaki Kise, Kiminobu Arima, Jun Kanno, Yoshiki Sugimura
  • Organizer: The 2010 American Urological Association (AUA) Annual Meeting
  • Place of Presentation: San Francisco
• [Presentation] Unique growth-inhibitory effects of subtype selective α1-adrenoceptor antagonists on human prostate cancer cells (2010)
  • Author(s): Yasuhide Hori, Kenichiro Ishii, Hideki Kanda, Kohei Nishikawa, Yuko Yoshio, Norihito Soga, Hideaki Kise, Kiminobu Arima, Jun Kanno, Yoshiki Sugimura
  • Organizer: The 2010 American Urological Association (AUA) Annual Meeting
  • Place of Presentation: San Francisco
• [Presentation] α1aアドレナリン受容体選択性遮断薬Silodosinによる癌微小環境を標的とした前立腺癌増殖抑制メカニズム (2010)
  • Author(s): 堀靖英、石井健一朗、神田英輝、西川晃平、吉尾裕子、曽我倫久人、木瀬英明、有馬公伸、杉村芳樹
  • Organizer: 第98回日本泌尿器科学会総会
  • Place of Presentation: 盛岡市
• [Presentation] 前立腺基底上皮細胞の生物学的特性:増殖因子と性ホルモンの影響 (2010)
  • Author(s): 吉尾裕子、石井健一朗、堀靖英、西川晃平、曽我倫久人、木瀬英明、有馬公伸、杉村芳樹
  • Organizer: 第98回日本泌尿器科学会総会
  • Place of Presentation: 盛岡市
• [Presentation] サブタイプ選択性α1アドレナリン受容体遮断薬による受容体非依存的な前立腺癌増殖抑制作用 (2010)
  • Author(s): 堀靖英、石井健一朗、神田英輝、西川晃平、吉尾裕子、曽我倫久人、木瀬英明、有馬公伸、杉村芳樹
  • Organizer: 第19回泌尿器科分子・細胞研究会
  • Place of Presentation: 神戸市
• [Presentation] エストロゲン様化学物質誘導性マウス前立腺基底上皮細胞の異常増殖におけるEGFRリガンドの作用 (2010)
  • Author(s): 吉尾裕子、石井健一朗、堀靖英、西川晃平、曽我倫久人、木瀬英明、有馬公伸、杉村芳樹
  • Organizer: 第19回泌尿器科分子・細胞研究会
  • Place of Presentation: 神戸市
• [Presentation] Heterogeneity of carcinoma-associated fibroblast-like differentiation in normal human prostatic fibroblasts (2010)
  • Author(s): 石井健一朗、堀靖英、溝上敦、山田泰司、有馬公伸、並木幹夫、杉村芳樹
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 癌間質を標的にした再燃前立腺癌に対する新規治療戦略 (2009)
  • Author(s): 石井健一朗(指定演題)
  • Organizer: 第4回 Basic Urology Research Seminar
  • Place of Presentation: 浅草
  • Year and Date: 2009-08-22
• [Presentation] 前立腺間質、正常上皮および癌間質間のネットワーク構成の比較-前立腺癌フィールドエフェクトの解析- (2009)
  • Author(s): 角田俊之、石井健一朗、杉村芳樹、内藤誠二(指定演題、石井が発表)
  • Organizer: 第25回前立腺シンポジウム
  • Place of Presentation: 品川
• [Presentation] Biological effects of fetal exposure to bisphenol A on urogenital sinus (2009)
  • Author(s): Kenichiro Ishii, Shigeki Arase, Katsuhide Igarashi, Kenichi Aisaki, Yuko Yoshio, Yasuhide Hori, Kohei Nishikawa, Norihito Soga, Hideaki Kise, Kiminobu Arima, Jun Kanno, Yoshiki Sugimura
  • Organizer: 19th Annual Fall Meeting of the Society for Basic Urologic Research (SBUR)
  • Place of Presentation: New Orleans
• [Presentation] Carcinoma-associated fibroblast-like differentiation of normal human prostatic fibroblasts (2009)
  • Author(s): 石井健一朗, 角田俊之, 堀靖英, 山田泰司, 有馬公伸, 杉村芳樹
  • Organizer: 第68回日本癌学会総会学術総会
  • Place of Presentation: 横浜市
• [Presentation] Unique growth-inhibitory effects of subtype selective alpha1-adrenoceptor antagonists on human prostate cancer cells (2009)
  • Author(s): 堀靖英, 石井健一朗, 山田泰司, 有馬公伸, 杉村芳樹
  • Organizer: 第68回日本癌学会総会学術総会
  • Place of Presentation: 横浜市
• [Presentation] ホルモン依存性喪失ヒト前立腺癌細胞モデルを用いた再燃前立腺癌の増殖メカニズム解析 (2009)
  • Author(s): 石井健一朗、井口和弘、深見和宏、吉尾裕子、堀靖英、西川晃平、曽我倫久人、木瀬英明、有馬公伸、平野和行、杉村芳樹
  • Organizer: 第28回日本アンドロロジー学会学術大会
  • Place of Presentation: 富山市
• [Presentation] A new therapeutic strategy for targeting tumor stroma in hormone-refractory prostate cancer cell growth under androgen ablation therapy (2009)
  • Author(s): Kenichiro Ishii, Tetsuya Imamura, Kazuhiro Iguchi, Shigeki Arase, Yuko Yoshio, Yasuhide Hori, Kiminobu Arima, Kazuyuki Hirano, Yoshiki Sugimura
  • Organizer: The 2009 American Urological Association (AUA) Annual Meeting
  • Place of Presentation: Chicago
• [Presentation] Stromal tenascin-C signal regulates mouse prostatic development and epithelial cell differentiation (2009)
  • Author(s): Kenichiro Ishii, Kyoko Imanaka-Yoshida, Tetsuya Imamura, Shigeki Arase, Yuko Yoshio, Yasuhide Hori, Kiminobu Arima, Toshimichi Yoshida, Yoshiki Sugimura
  • Organizer: The 2009 American Urological Association (AUA) Annual Meeting
  • Place of Presentation: Chicago
• [Presentation] TGFα過発現マウス前立腺の病理組織学的解析 (2009)
  • Author(s): 石井健一朗、吉尾裕子、荒瀬栄樹、今村哲也、堀靖英、有馬公伸、杉村芳樹
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山市
• [Presentation] マウスゼノグラフトモデルを用いた前立腺肥大症組織に対する各種薬剤の影響評価 (2009)
  • Author(s): 今村哲也、石井健一朗、荒瀬栄樹、吉尾裕子、堀靖英、曽我倫久人、木瀬英明、有馬公伸、杉村芳樹
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山市
• [Presentation] ビスフェノールA経胎盤曝露によりマウス泌尿生殖洞で発現変動する性分化関連遺伝子群の同定 (2009)
  • Author(s): 荒瀬栄樹 、石井健一朗、五十嵐勝秀、相崎健一、小倉友二、今村哲也、吉尾裕子、有馬公伸、菅野純、杉村芳樹
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山市
• [Presentation] A new therapeutic strategy for targeting tumor stroma in hormone-refractory prostate cancer cell growth under androgen ablation therapy (2009)
  • Author(s): Ishii K, Imamura T, Iguchi K, Arase S, Yoshio Y, Hori Y, Arima K, Hirano K, Sugimura Y
  • Organizer: The 2009 American Urological Association (AUA) Annual Meeting
  • Place of Presentation: Chicago, IL, USA
• [Book] 泌尿器外科 23(8)("前立腺間質、正常上皮および癌間質間のネットワーク構成の比較-前立腺癌フィールドエフェクトの解析-") (2010)
  • Author(s): 石井健一朗、角田俊之、内藤誠二、杉村芳樹