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Comprehensive analysis of metalloproteinases in cancer-associated fibroblasts

Research Project

Project/Area Number 25860276
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionKeio University

Principal Investigator

Shimoda Masayuki  慶應義塾大学, 医学部, 講師 (70383734)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsがん / 線維芽細胞 / メタロプロテアーゼ
Outline of Final Research Achievements

Carcinoma-associated fibroblasts (CAFs), frequently observed in tumor stroma, are more capable of maintaining cancer stem cells and promoting tumor growth and angiogenesis through their interactions with carcinoma cells. In this study, we performed comprehensive analysis of metalloproteinases in tumor stroma and CAFs. We found that, in stroma associated with human cancer, several metalloproteinases were significantly upregulated, whereas there was a trend towards decreased expression of tissue inhibitors of metalloproteinases (TIMPs). By analyzing CAF microarray datasets, we identified several candidates for CAF-specific metalloproteinases. CAFs also secreted exosomes containing more metalloproteinases including ADAM10 compared to normal adjacent fibroblasts. These data suggest that dysregulation of metalloproteinases in CAFs may contribute to their tumor-propagating ability in patients.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2016 2015 2014 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Tumor suppression by stromal TIMPs2016

    • Author(s)
      Shimoda M, Jackson HW and Khokha R
    • Journal Title

      Cellular and Molecular Oncology

      Volume: - Issue: 3 Pages: e975082-e975082

    • DOI

      10.4161/23723556.2014.975082

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epithelial cell-derived a disintegrin and metalloproteinase-17 confers resistance to colonic inflammation through EGFR activation2016

    • Author(s)
      Shimoda M, Horiuchi K, Sasaki A, Tsukamoto T, Okabayashi K, Hasegawa H, Kitagawa Y and Okada Y
    • Journal Title

      EBioMedicine

      Volume: 5 Pages: 114-24

    • DOI

      10.1016/j.ebiom.2016.02.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of the Timp gene family is sufficient for the acquisition of the CAF-like cell state.2014

    • Author(s)
      Shimoda M, Principe S, Jackson HW, Luga V, Fang H, Molyneux SD, Shao YW, Aiken A, Waterhouse PD, Karamboulas C, Hess FM, Ohtsuka T, Okada Y, Ailles L, Ludwig A, Wrana JL, Kislinger T and Khokha R
    • Journal Title

      Nature Cell Biology

      Volume: 16 Pages: 889-901

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] メタロプロテアーゼによる組織内微小環境因子代謝2014

    • Author(s)
      下田将之、岡田保典
    • Journal Title

      病理と臨床

      Volume: 32 Pages: 24-30

    • Related Report
      2013 Research-status Report
  • [Presentation] 病的組織におけるメタロプロテアーゼの機能解析研究2015

    • Author(s)
      下田将之
    • Organizer
      日本病理学会総会
    • Place of Presentation
      名古屋国際会場(愛知県名古屋)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 癌間質線維芽細胞形質獲得におけるTIMP分子の機能解析2014

    • Author(s)
      下田将之、Rama Khokha
    • Organizer
      第103回病理学会総会
    • Place of Presentation
      広島
    • Year and Date
      2014-04-24
    • Related Report
      2014 Research-status Report
  • [Book] 実験医学2014

    • Author(s)
      下田将之、岡田保典
    • Total Pages
      9
    • Publisher
      羊土社
    • Related Report
      2014 Research-status Report
  • [Remarks] 慶應義塾大学医学部 病理学教室

    • URL

      http://www.keio-pathology.net/

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Remarks] 慶應義塾大学医学部 病理学教室

    • URL

      http://www.keio-pathology.net/index.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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