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Mechanisms of prostate cancer heterogeneity induced by disease-associated reprogramming

Research Project

Project/Area Number 15K10583
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Arima Kiminobu  三重大学, 医学系研究科, 准教授 (10175995)

Co-Investigator(Kenkyū-buntansha) 佐々木 豪  三重大学, 医学部附属病院, 助教 (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) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords前立腺 / 疾患関連リプログラミング / 間質リモデリング / 線維芽細胞の多様性 / 前立腺癌患者由来線維芽細胞 / 前立腺幹・前駆細胞 / in vitro共培養実験 / in vivo共移植実験
Outline of Final Research Achievements

Deregulation of epithelial-stromal interactions is considered to play a critical role in the initiation of prostate cancer (PCa). Fibroblasts secret a number of growth factors, cytokines, and miRNAs that affect cellular differentiation of epithelial cells. In this study, we investigated the effects of fibroblasts on the expression of tumor suppressor genes in non-transformed human prostatic epithelial cell line BPH-1 in vitro and in vivo. In in vitro co-culture experiments, mRNA expression of GSTP1 in BPH-1 cells was decreased by co-culturing with fibroblasts. In in vivo co-inoculation experiments, mRNA expression of GSTP1 was quite low in infiltrating solid branching epithelial cords surrounding tenascin-C-expressing fibroblasts. Our data showed that GSTP1 in BPH-1 cells were highly disturbed by interactions with fibroblasts. The use of PCa patients-derived fibroblasts may allow us to investigate the characteristics of aggressive fibroblasts in the initiation of PCa.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (21 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results) Presentation (17 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Role of stromal paracrine signals in proliferative diseases of the aging human prostate.2018

    • Author(s)
      Ishii K, Takahashi S, Sugimura Y, Watanabe M.
    • Journal Title

      Journal of Clinical Medicine

      Volume: 7 Pages: 68-88

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human prostate cancer cells.2018

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

      Journal of Cancer Research and Clinical Oncology

      Volume: 144 Issue: 1 Pages: 89-98

    • DOI

      10.1007/s00432-017-2536-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [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
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Aberrant activation of androgen-low-sensitive prostate cancer cells-fibroblasts interactions under androgen deprivation2017

    • Author(s)
      石井健一朗、井口和弘、梶原進也、加藤 学、有馬公伸、白石泰三、杉村芳樹
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Role of epithelial-fibroblasts interactions in initiation of prostate cancer2017

    • Author(s)
      梶原進也、石井健一朗、加藤 学、有馬公伸、杉村芳樹
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 前立腺間質構造の多様性による前立腺癌不均一性の獲得機構2017

    • Author(s)
      石井健一朗、梶原進也、佐々木 豪、三木 学、加藤 学、神田英輝、有馬公伸、杉村芳樹
    • Organizer
      第105回 日本泌尿器科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 前立腺癌進展におけるリガンド非依存的なアンドロゲン受容体活性化分子機構2017

    • Author(s)
      松尾いづみ、石井健一朗、佐々木 豪、三木 学、梶原進也、加藤 学、神田英輝、有馬公伸、杉村芳樹
    • Organizer
      第105回 日本泌尿器科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 前立腺癌微小環境予測における前立腺MRI ADC scoreの有用性2017

    • Author(s)
      加藤 学、石井健一朗、梶原進也、三木 学、神田英輝、有馬公伸、白石泰三、杉村芳樹
    • Organizer
      第105回 日本泌尿器科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膀胱癌における癌―間質相互作用2017

    • Author(s)
      三木 学、石井健一朗、加藤 学、佐々木 豪、梶原進也、神田英輝、有馬公伸、白石泰三、杉村芳樹
    • Organizer
      第105回 日本泌尿器科学会総会
    • Related Report
      2017 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status Report
  • [Presentation] A new insight of cell-cell interactions in tumor stroma of prostate cancer2015

    • Author(s)
      Kenichiro Ishii, Takeshi Sasaki, Manabu Miki, Manabu Kato, Hideki Kanda, Kiminobu Arima, Atsushi Mizokami, 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] 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] Effect of LPA receptor 1 antagonist on bone metastatic prostate cancer2015

    • Author(s)
      Manabu Miki, Hideki Kanda, Kenichiro Ishii, Takeshi Sasaki, 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] 線維芽細胞に作用する既存医薬品のドラッグ・リポジショニングによる前立腺癌治療戦略2015

    • Author(s)
      石井 健一朗、佐々木 豪、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] 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] LPA受容体(LPAR)1拮抗薬の有用性を念頭にした、前立腺癌間質を含む各細胞株におけるLPAR発現の検討2015

    • Author(s)
      三木 学、神田 英輝、佐々木 豪、石井 健一朗、有馬 公伸、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

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Published: 2015-04-16   Modified: 2019-03-29  

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