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Identification and functional analysis of a liver stromal cell-derived factor contributing to liver metastasis of colorectal cancer cells

Research Project

Project/Area Number 18K08693
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionMicrobial Chemistry Research Foundation

Principal Investigator

Tomokazu Ohishi  公益財団法人微生物化学研究会, 微生物化学研究所 沼津支所, 主任研究員 (50442546)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsがんー間質相互作用 / がん-間質相互作用 / 大腸がん / がん-間質相互作用 / 大腸がん肝転移 / がん関連線維芽細胞
Outline of Final Research Achievements

In this study, we tried to identify a novel molecule, which is involved in the liver metastasis of colorectal cancer. We sought the possibility of a new therapeutic strategy targeting the molecule for the treatment of liver metastasis of colorectal cancer. 1)Plasminogen activator inhibitor-1 (PAI-1), a negative regulator of the fibrinolytic pathway is identified as a candidate of promoting factor of liver metastasis of colorectal cancer. 2) Treatment of PAI-1 inhibitor suppressed liver metastasis of colorectal cancer in a mouse model of liver metastasis of colorectal cancer. 3)Similarly, PAI-1 knockout mice suppressed liver metastasis of colorectal cancer compared with wild-type mice.
Taken together, PAI-1 promotes liver metastasis of colorectal cancer and inhibition of PAI-1 may suppress liver metastasis of colorectal cancer.

Academic Significance and Societal Importance of the Research Achievements

大腸がんは国内罹患数が最も高いがんであり、早急な対応が急務である。大腸がんの転移は患者の予後不良に直結し、約7~8割を占める大腸がん肝転移の制御が重要である。現在、抗上皮成長因子受容体(EGFR)抗体薬が推奨されていないRAS変異型の大腸がん患者の存在が問題となっており、新たな治療戦略が求められてきた。我々が見出したPAI-1は大腸がん肝転移を促進する因子であることから、新たな治療標的として考えられる。その阻害剤や中和抗体は、抗EGFR抗体薬不応性のがんにも適用できると見込まれ、社会的意義は大きい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2021 2020 2019 2018 Other

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (6 results) Book (1 results) Remarks (1 results)

  • [Journal Article] The Beneficial Effects of Principal Polyphenols from Green Tea, Coffee, Wine, and Curry on Obesity2021

    • Author(s)
      Ohishi Tomokazu、Fukutomi Ryuuta、Shoji Yutaka、Goto Shingo、Isemura Mamoru
    • Journal Title

      Molecules

      Volume: 26 Issue: 2 Pages: 453-453

    • DOI

      10.3390/molecules26020453

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of mitochondria ATP synthase suppresses prostate cancer growth through reduced insulin-like growth factor-1 secretion by prostate stromal cells2020

    • Author(s)
      Tomokazu Ohishi, Hikaru Abe, Chiharu Sakashita, Uzma Saqib, Mirza S. Baig, Shun‐ichi Ohba, Hiroyuki Inoue, Takumi Watanabe, Masakatsu Shibasaki, Manabu Kawada
    • Journal Title

      Int. J. Cancer

      Volume: 146 Issue: 12 Pages: 3474-3484

    • DOI

      10.1002/ijc.32959

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tumor-derived exosomes in the regulation of macrophage polarization2020

    • Author(s)
      Baig Mirza S.、Roy Anjali、Rajpoot Sajjan、Liu Dongfang、Savai Rajkumar、Banerjee Sreeparna、Kawada Manabu、Faisal Syed M.、Saluja Rohit、Saqib Uzma、Ohishi Tomokazu、Wary Kishore K.
    • Journal Title

      Inflammation Research

      Volume: 69 Issue: 5 Pages: 435-451

    • DOI

      10.1007/s00011-020-01318-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody H2Mab-19 Exerts Antitumor Activity in Mouse Colon Cancer Xenografts2020

    • Author(s)
      Kato Yukinari、Ohishi Tomokazu、Takei Junko、Nakamura Takuro、Sano Masato、Asano Teizo、Sayama Yusuke、Hosono Hideki、Kawada Manabu、Kaneko Mika K.
    • Journal Title

      Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

      Volume: 39 Issue: 4 Pages: 123-128

    • DOI

      10.1089/mab.2020.0009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-Metastatic Activity of an Anti-EGFR Monoclonal Antibody against Metastatic Colorectal Cancer with KRAS p.G13D Mutation2020

    • Author(s)
      Ohishi Tomokazu、Kato Yukinari、Kaneko Mika K.、Ohba Shun-ichi、Inoue Hiroyuki、Harakawa Akiko、Kawada Manabu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 17 Pages: 6037-6037

    • DOI

      10.3390/ijms21176037

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The anti-EpCAM monoclonal antibody EpMab-16 exerts antitumor activity in a mouse model of colorectal adenocarcinoma2020

    • Author(s)
      Hosono H, Ohishi T, Takei J, Asano T, Sayama Y, Kawada M, Kaneko MK, Kato Y
    • Journal Title

      Oncol Lett

      Volume: 20 Issue: 6 Pages: 383-383

    • DOI

      10.3892/ol.2020.12246

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a Small Compound Targeting PKM2-Regulated Signaling Using 2D Gel Electrophoresis-Based Proteome-wide CETSA2020

    • Author(s)
      Nagasawa Ikuko、Muroi Makoto、Kawatani Makoto、Ohishi Tomokazu、Ohba Shun-ichi、Kawada Manabu、Osada Hiroyuki
    • Journal Title

      Cell Chemical Biology

      Volume: 27 Issue: 2 Pages: 1-11

    • DOI

      10.1016/j.chembiol.2019.11.010

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-CD133 Monoclonal Antibody CMab-43 Exerts Antitumor Activity in a Mouse Xenograft Model of Colon Cancer2019

    • Author(s)
      Kato Yukinari、Ohishi Tomokazu、Yamada Shinji、Itai Shunsuke、Furusawa Yoshikazu、Sano Masato、Nakamura Takuro、Kawada Manabu、Kaneko Mika K.
    • Journal Title

      Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

      Volume: 38 Issue: 2 Pages: 75-78

    • DOI

      10.1089/mab.2019.0002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody H2Mab-41 Exerts Antitumor Activity in a Mouse Xenograft Model of Colon Cancer2019

    • Author(s)
      Kato Yukinari、Ohishi Tomokazu、Yamada Shinji、Itai Shunsuke、Takei Junko、Sano Masato、Nakamura Takuro、Harada Hiroyuki、Kawada Manabu、Kaneko Mika K.
    • Journal Title

      Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

      Volume: 38 Issue: 4 Pages: 157-161

    • DOI

      10.1089/mab.2019.0017

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 大腸がん肝転移を支持する肝臓間質細胞由来因子の同定とその抑制2019

    • Author(s)
      大石智一、大庭俊一、川田学
    • Organizer
      第23回日本がん分子標的治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 大石智一、川田学2019

    • Author(s)
      肝臓間質細胞由来因子を標的とした大腸がん肝転移の抑制
    • Organizer
      第28回日本がん転移学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 大石智一、川田学2019

    • Author(s)
      Targeting tumor-stromal cell interactions for treatment strategy of colorect al cancer liver metastasis
    • Organizer
      第78回日本癌学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 大腸がん肝転移に関与する肝臓間質細胞由来因子の同定2018

    • Author(s)
      大石智一、大庭俊一、川田学
    • Organizer
      第22回日本がん分子標的治療学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 大腸がん肝転移に寄与する肝臓間質細胞由来因子の同定2018

    • Author(s)
      大石智一、川田学
    • Organizer
      第27回日本がん転移学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of a treatment strategy for liver metastasis of CRCs by targeting a factor secreted from liver stromal cells2018

    • Author(s)
      大石智一、川田学
    • Organizer
      第77回日本癌学会学術集会
    • Related Report
      2018 Research-status Report
  • [Book] 新版改訂 微生物と免疫2020

    • Author(s)
      林修 編著 石井恭子 石橋健一 碓井之雄 江崎一子 大石智一 太田利子 熊谷優子 中屋祐子 共著
    • Total Pages
      184
    • Publisher
      建帛社
    • ISBN
      9784767906850
    • Related Report
      2020 Annual Research Report
  • [Remarks] 微生物化学研究所 HP

    • URL

      https://www.bikaken.or.jp

    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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