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Molecular mechanisms of ligand-independent androgen receptor activation in development and progression of prostate cancer

Research Project

Project/Area Number 26462408
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionMie University

Principal Investigator

Sugimura Yoshiki  三重大学, 医学系研究科, 教授 (90179151)

Co-Investigator(Kenkyū-buntansha) 神田 英輝  三重大学, 医学部附属病院, 講師 (10397507)
佐々木 豪  三重大学, 医学部附属病院, 医員 (20644941)
白石 泰三  三重大学, 医学系研究科, 客員教授 (30162762)
石井 健一朗  三重大学, 医学系研究科, 助教 (90397513)
加藤 学  三重大学, 医学部附属病院, 助教 (60626117)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords前立腺癌 / 癌関連線維芽細胞 / アンドロゲン受容体 / 前立腺特異抗原 / 前立腺癌間質標的療法 / 癌間質線維芽細胞
Outline of Final Research Achievements

Tumor stroma surrounding prostate cancer (PCa) cells is enriched in fibroblasts secreting androgen receptor (AR)-activating factors. Thus, fibroblast-dependent AR activation in PCa cells under androgen deprivation therapy (ADT) may play an important role in progression of castration-resistant prostate cancer (CRPC). In this study, we investigated the role of fibroblasts in AR activation of PCa cells differing in androgen sensitivity. In the condition of co-cultures with fibroblasts, PSA production was directly increased in E9 cells but not in F10 and AIDL cells. In E9 cells + pcPrF-M5 group, tumor growth became diminished post ADT but serum PSA was gradually increased even post ADT. Here our results have demonstrated that fibroblast-dependent AR activation under ADT showed diverse effects in PCa cells differing in androgen sensitivity. In a certain androgen-low-sensitive PCa cells, fibroblast-dependent AR activation may progress to CRPC.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (24 results)

All 2017 2016 2015 2014

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 3 results,  Open Access: 2 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Combination treatment with naftopidil increases the efficacy of radiotherapy in PC-3 human prostate cancer cells2017

    • Author(s)
      Iwamoto Y, Ishii K, Kanda H, Kato M, Miki M, Kajiwara S, Arima K, Shiraishi T, Sugimura Y
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: 印刷中 Issue: 6 Pages: 933-939

    • DOI

      10.1007/s00432-017-2367-9

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Low serum dehydroepiandrosterone examined by liquid chromatography-tandem mass spectrometry correlates with poor prognosis in hormone-naïve prostate cancer.2016

    • Author(s)
      Miyoshi Y, Uemura H, Umemoto S, Sakamaki K, Taguri M, Suzuki K, Shibata Y, Masumori N, Ichikawa T, Mizokami A, Sugimura Y, Nonomura N, Sakai H, Honma S, Harada M, Kubota Y.
    • Journal Title

      Prostate

      Volume: 76 Issue: 4 Pages: 376-382

    • DOI

      10.1002/pros.23129

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fibroblasts prolong serum prostate-specific antigen decline after androgen deprivation therapy in prostate cancer2016

    • Author(s)
      Sasaki T, Ishii K, Iwamoto Y, Kato M, Miki M, Kanda H, Arima K, Shiraishi T, Sugimura Y
    • Journal Title

      Laboratory Investigations

      Volume: 96 Issue: 3 Pages: 338-349

    • DOI

      10.1038/labinvest.2015.136

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of a new pharmacological activity of the phenylpiperazine derivative naftopidil: tubulin-binding drug2015

    • Author(s)
      Ishii K and Sugimura Y
    • Journal Title

      Journal of Chemical Biology

      Volume: 8 Issue: 1 Pages: 5-9

    • DOI

      10.1007/s12154-014-0122-0

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Essential roles of epithelial bone morphogenetic protein signaling during prostatic development2014

    • Author(s)
      A. Omori, S. Miyagawa, Y. Ogino, M. Harada, K. Ishii, Y. Sugimura, H. Ogino, N. Nakagata and G. Yamada
    • Journal Title

      Endocrinology

      Volume: 155 Issue: 7 Pages: 2534-44

    • DOI

      10.1210/en.2013-2054

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High testosterone levels in prostate tissue obtained by needle biopsy correlate with poor-prognosis factors in prostate cancer patients.2014

    • Author(s)
      Miyoshi Y, Uemura H, Umemoto S, Sakamaki K, Morita S, Suzuki K, Shibata Y, Masumori N, Ichikawa T, Mizokami A, Sugimura Y, Nonomura N, Sakai H, Honma S, Harada M, Kubota Y.
    • Journal Title

      BMC Cancer

      Volume: Sep 26 Issue: 1 Pages: 717-717

    • DOI

      10.1186/1471-2407-14-717

    • NAID

      120006986365

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The usefulness of diffusion-weighted magnetic resonance imaging in bladder cancer staging and functional analysis2014

    • Author(s)
      Yamada Y, Kobayashi S, Isoshima S, Arima K, Sakuma H, Sugimura Y
    • Journal Title

      J Cancer Res Ther

      Volume: 10 Issue: 4 Pages: 878-882

    • DOI

      10.4103/0973-1482.138225

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 前立腺癌微小環境における間質性細胞間相互作用の異常活性化2016

    • Author(s)
      石井健一朗、加藤 学、有馬公伸、溝上 敦、白石泰三、杉村芳樹
    • Organizer
      第75回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] A new insight of cell-cell interactions in tumor stroma of prostate cancer2016

    • Author(s)
      Kenichiro Ishii, Takeshi Sasaki, Manabu Miki, Manabu Kato, Hideki Kanda, Kiminobu Arima, Atsushi Mizokami, Taizo Shiraishi, Yoshiki Sugimura
    • Organizer
      第105回 日本病理学会総会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] The exploration of the order in the heterogeneity of prostate cancer-associated stroma environment2016

    • Author(s)
      Manabu Kato, Takeshi Sasaki, Kenichiro Ishii, Manabu Miki, Kohei Nishikawa, Kiminobu Arima, Taizo Shiraishi, Neil Bhowmick, Yoshiki Sugimura
    • Organizer
      111st American Urological Association Annual meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2016-05-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Fibroblasts prolong serum prostate-specific antigen decline after androgen deprivation therapy in prostate cancer2016

    • Author(s)
      Takeshi Sasaki, Kenichiro Ishii, Manabu Miki, Hideki Kanda, Kiminobu Arima, Taizo Shiraishi, Yoshiki Sugimura
    • Organizer
      111st American Urological Association Annual meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2016-05-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] A new insight of cell-cell interactions in tumor stroma of prostate cancer2016

    • Author(s)
      Kenichiro Ishii, Takeshi Sasaki, Manabu Miki, Manabu Kato, Hideki Kanda, Kiminobu Arima, Taizo Shiraishi, Yoshiki Sugimura
    • Organizer
      111st American Urological Association Annual meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2016-05-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 前立腺癌関連線維芽細胞の自律的増殖機構2016

    • Author(s)
      石井健一朗、佐々木 豪、三木 学、加藤 学、神田英輝、有馬公伸、溝上 敦、白石泰三、杉村芳樹
    • Organizer
      第104回 日本泌尿器科学会総会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-04-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] 細胞表面タンパクによる前立腺癌間質細胞の不均一性の検討2016

    • Author(s)
      加藤 学、三木 学、石井健一朗、加藤桃子、梶原進也、吉川昌希、矢﨑順二、吉尾裕子、長谷川嘉弘、神田英輝、金井優博、有馬公伸、杉村芳樹、Neil A Bhowmick
    • Organizer
      第104回 日本泌尿器科学会総会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-04-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] 既存医薬品のオフターゲット効果を活用した去勢抵抗性前立腺癌治療への新規アプローチ2016

    • Author(s)
      松岡いづみ、石井健一朗、佐々木 豪、三木 学、加藤 学、神田英輝、有馬公伸、白石泰三、杉村芳樹
    • Organizer
      第104回 日本泌尿器科学会総会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-04-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] 前立腺癌骨転移に対するリソホスファチジン酸(LPA)受容体拮抗薬の影響2016

    • Author(s)
      三木 学、神田英輝、石井健一朗、佐々木 豪、加藤 学、有馬公伸、白石泰三、杉村芳樹
    • Organizer
      第104回 日本泌尿器科学会総会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-04-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] 前立腺癌微小環境における細胞間相互作用2015

    • Author(s)
      石井健一朗、杉村芳樹
    • Organizer
      第31回 前立腺シンポジウム
    • Place of Presentation
      TKP品川カンファレンスセンター(東京都・港区)
    • Year and Date
      2015-12-12
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Fibroblasts prolong serum prostate specific antigen decline after androgen deprivation therapy in prostate cancer2015

    • Author(s)
      Takeshi Sasaki, Kenichiro Ishii, Manabu Miki, Manabu Kato, Hideki Kanda, Kiminobu Arima, Taizo Shiraishi, Yoshiki Sugimura
    • Organizer
      25th Annual Fall Meeting of the Society for Basic Urologic Research
    • Place of Presentation
      Fort Lauderdale, FL, USA
    • Year and Date
      2015-11-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A new insight of cell-cell interactions in tumor stroma of prostate cancer2015

    • Author(s)
      Kenichiro Ishii, Takeshi Sasaki, Taizo Shiraishi, Yoshiki Sugimura
    • Organizer
      第74回 日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Stromal interleukin-6 acts as paracrine angiogenic cytokine in prostate cancer microenvironment2015

    • Author(s)
      Kenichiro Ishii, Takeshi Sasaki, Manabu Miki, Kazuhiro Iguchi, Atsushi Mizokami, Hideki Kanda, Kiminobu Arima, Taizo Shiraishi, Yoshiki Sugimura
    • Organizer
      第104回 日本病理学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report
  • [Presentation] 前立腺癌微小環境の不均一性に基づくアンドロゲン除去療法後の血中PSA動態2015

    • Author(s)
      佐々木 豪、石井健一朗、三木 学、神田英輝、有馬公伸、白石泰三、杉村芳樹
    • Organizer
      第103回 日本泌尿器科学会総会
    • Place of Presentation
      ANAクラウンプラザホテル金沢(石川県・金沢市)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Investigation of New Therapeutic Targets In Bladder Cancer Microenvironment2014

    • Author(s)
      Manabu Miki, Takeshi Sasaki, Kenichiro Ishii, Manabu Kato, Hideki Kanda, Kiminobu Arima, Taizo Shiraishi, Yoshiki Sugimura
    • Organizer
      2014 Society for Basic Urologic Research (SBUR) Fall Symposium
    • Place of Presentation
      Dallas, USA
    • Year and Date
      2014-11-13 – 2014-11-16
    • Related Report
      2014 Research-status Report
  • [Presentation] 前立腺のバイオロジー:発生・分化・増殖2014

    • Author(s)
      石井健一朗、杉村芳樹
    • Organizer
      第4回 前立腺生物学シンポジウム
    • Place of Presentation
      三重県鳥羽市・鳥羽国際ホテル
    • Year and Date
      2014-06-26 – 2014-06-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Fibroblasts in prostate cancer microenvironment prescribe serum prostate-specific antigen kinetics after hormone therapy2014

    • Author(s)
      Takeshi Sasaki, Kenichiro Ishii, Hdeki Kanda, Yasushi Yamada, Kiminobu Arima, Taizo Shiraishi, Yoshiki Sugimura
    • Organizer
      The 2014 American Urological Association (AUA) Annual Meeting
    • Place of Presentation
      Orland, USA
    • Year and Date
      2014-05-16 – 2014-05-21
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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