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Effects of prostate cancer associated fibroblasts in the expression of aberrant andorgen splicing variants in prostate cancer cells

Research Project

Project/Area Number 18K16690
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56030:Urology-related
Research InstitutionMie University

Principal Investigator

Sasaki Takeshi  三重大学, 医学部附属病院, 助教 (20644941)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords前立腺癌 / 癌関連線維芽細胞 / スプライシングバリアント / 線維芽細胞 / 去勢抵抗性前立腺癌 / 癌間質
Outline of Final Research Achievements

Expression of androgen receptor (AR) splice variant (AR-V) has been identified as the mechanism associated with the development of castration-resistant prostate cancer (PCa). However, the mechanisms mediating increased expression of aberrant AR-Vs in PCa are still largely unknown.The purpose of this study was to identify if prostate fibroblasts in tumor stroma induces the expression of aberrant AR-Vs in PCa.We investigated the mRNA expression of AR, PSA, AR-V1, AR-V567es, AR-V7, and its target genes by co-cultured with three fibroblasts lines (PrSC, pcPrFs-M28, and pcPrFs-M31).mRNA expression of AR, AR-V1, and AR-V7 in LNCaP cells were increased by co-culture with pcPrFs-M28 but not with PrSC and pcPrFs-M31.Primary cultured prostate fibroblasts from prostate cancer specimens increased expression of aberrant AR-V1 and AR-V7 in PCa cells. Prostate fibroblasts in tumor stroma may be a target for the treatment preventing the expression of aberrant AR-Vs in PCa.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、前立腺癌間質の多様性に着目した、前立腺癌関連線維芽細胞(CAFs)由来パラクライン刺激による前立腺癌細胞のアンドロゲン受容体スプライシングバリアント(ARVs)発現修飾作用の可能性が示唆された。治療前のCAFsの性状解析を行い、CAFs由来ARVs発現誘導因子を阻害することで癌細胞のARVs発現上昇を阻止し、長期に治療奏効性を維持できる可能性が示された。これまでの画一的なホルモン治療と異なり、個々の患者に合わせ、癌間質をターゲットとした治療薬の併用というオーダーメイド医療の確立が期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Pirfenidone, an Anti-Fibrotic Drug, Suppresses the Growth of Human Prostate Cancer Cells by Inducing G1 Cell Cycle Arrest2019

    • Author(s)
      Ishii Kenichiro、Sasaki Takeshi、Iguchi Kazuhiro、Kato Manabu、Kanda Hideki、Hirokawa Yoshifumi、Arima Kiminobu、Watanabe Masatoshi、Sugimura Yoshiki
    • Journal Title

      Journal of Clinical Medicine

      Volume: 8 Issue: 1 Pages: 44-44

    • DOI

      10.3390/jcm8010044

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of fibroblast-dependent androgen receptor activation in prostate cancer cells is involved in the mechanism of acquired resistance to castration2019

    • Author(s)
      Ishii K, Matsuoka I, Sasaki T, Nishikawa K, Kanda H, Imai H, Hirokawa Y, Iguchi K, Arima K, Sugimura Y
    • Journal Title

      Journal of Clinical Medicine

      Volume: 8 Issue: 9 Pages: 1379-1379

    • DOI

      10.3390/jcm8091379

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tyrosine kinase inhibitor therapy prescribed for non-urologic diseases can modify PSA titers in urology patients2018

    • Author(s)
      Sasaki Takeshi、Franco Omar E.、Ohishi Kohshi、Filipovich Yana、Ishii Kenichiro、Crawford Susan E.、Takahashi Naoto、Katayama Naoyuki、Sugimura Yoshiki、Hayward Simon W.
    • Journal Title

      The Prostate

      Volume: 79 Issue: 3 Pages: 259-264

    • DOI

      10.1002/pros.23730

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Importance of Time to Prostate-Specific Antigen (PSA) Nadir after Primary Androgen Deprivation Therapy in Hormone-Naïve Prostate Cancer Patients.2018

    • Author(s)
      Sasaki T, Sugimura Y
    • Journal Title

      J Clin Med

      Volume: 7 Issue: 12 Pages: 565-565

    • DOI

      10.3390/jcm7120565

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predicting the tumorigenic phenotype of human bladder cancer cells by combining with fetal rat mesenchyme2018

    • Author(s)
      Miki Manabu、Ishii Kenichiro、Sasaki Takeshi、Kato Manabu、Kajiwara Shinya、Kanda Hideki、Arima Kiminobu、Hirokawa Yoshifumi、Watanabe Masatoshi、Sugimura Yoshiki
    • Journal Title

      Urologic Oncology: Seminars and Original Investigations

      Volume: 36 Issue: 10 Pages: 472-472

    • DOI

      10.1016/j.urolonc.2018.07.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin-6 induces VEGF secretion from prostate cancer cells in a manner independent of androgen receptor activation2018

    • Author(s)
      Ishii Kenichiro、Sasaki Takeshi、Iguchi Kazuhiro、Kajiwara Shinya、Kato Manabu、Kanda Hideki、Hirokawa Yoshifumi、Arima Kiminobu、Mizokami Atsushi、Sugimura Yoshiki
    • Journal Title

      The Prostate

      Volume: 78 Issue: 11 Pages: 849-856

    • DOI

      10.1002/pros.23643

    • Related Report
      2018 Research-status 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
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] チロシンキナーゼ阻害剤、ニロチニブによる前立腺癌細胞に対するオフターゲット効果.2019

    • Author(s)
      佐々木 豪、大石晃嗣、石井健一朗、高橋直人、片山直之、杉村芳樹
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 前立腺癌における癌関連線維芽細胞性状解析の臨床的有用性2019

    • Author(s)
      佐々木 豪、大和俊介、渡邉晋、杉野友亮、加藤学、舛井覚、西川晃平、吉尾裕子、神田英輝
    • Organizer
      第69回日本泌尿器科学会中部総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Long-term leptin administration reduces prostatic epithelial hyperplasia in the obob mouse model2018

    • Author(s)
      Takeshi Sasaki, Omar E. Franco, Yana Filipovich, LaTayia Aaron, Philip Fitchev, Douglas W. Strand, Susan E. Crawford, Simon W. Hayward
    • Organizer
      AUA - 第113回米国泌尿器学会議
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遺伝的肥満ob/obマウス前立腺上皮過形成における長期レプチン投与の影響2018

    • Author(s)
      佐々木豪、杉村芳樹、Simon W. Hayward
    • Organizer
      第106回日本泌尿器科学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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