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Analysis of cancer-associated fibroblasts from the perspective of proteinases and epigenetics

Research Project

Project/Area Number 16K08719
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionKeio University

Principal Investigator

SHIMODA MASAYUKI  慶應義塾大学, 医学部(信濃町), 講師 (70383734)

Co-Investigator(Kenkyū-buntansha) 大塚 崇  東京慈恵会医科大学, 医学部, 教授 (40306717)
Research Collaborator KANAI Yae  
OKADA Yasunori  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsがん / 線維芽細胞 / 腫瘍間質 / 網羅的解析 / プロテアーゼ / エピゲノム / がん関連線維芽細胞
Outline of Final Research Achievements

Cancer-associated fibroblasts (CAFs) within the tumor stroma are known to acquire activated phenotype and have been shown to stimulate tumor cell proliferation, elevate tumor cell invasion and boost angiogenesis. However, CAFs are also thought to derive from multiple origins and make up a heterogeneous population of cells, it is an important question to understand the unique roles of the different subpopulations of CAFs. In this project, we evaluated various CAF lines by analyzing both their biological tumor-promoting properties and gene expression patterns and sought to identify gene signatures characterizing functionally active CAFs. In these analyses, we identified several genes related to cancer progression increased in functionally active CAFs which would be useful for understanding molecular pathways induced in CAFs. Stromal cell-derived proteinases are also involved in tumor progression and might be potential targets for cancer therapy.

Academic Significance and Societal Importance of the Research Achievements

CAFは腫瘍進展を手助けするとともに治療に対する抵抗性を強めることから、今後の新たな治療標的の一つとして注目されているものの、CAFは様々な細胞に由来しその多様性から具体的な治療法の確立に至っていないのが現状である。本研究で得られる成果は、生物学的に意義のあるCAF細胞集団を同定しその性質を明らかにすることで、CAFを標的とした新規治療法や機能的分子病理診断の開発に貢献する可能性があると考えている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Invited: 2 results)

  • [Journal Article] Extracellular vesicle-associated MMPs: A modulator of the tissue microenvironment2019

    • Author(s)
      Shimoda Masayuki
    • Journal Title

      Advances in Clinical Chemistry

      Volume: 88 Pages: 35-66

    • DOI

      10.1016/bs.acc.2018.10.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ADAM9 is over-expressed in human ovarian clear cell carcinomas and suppresses cisplatin-induced cell death2018

    • Author(s)
      Ueno Mari、Shiomi Takayuki、Mochizuki Satsuki、Chijiiwa Miyuki、Shimoda Masayuki、Kanai Yae、Kataoka Fumio、Hirasawa Akira、Susumu Nobuyuki、Aoki Daisuke、Okada Yasunori
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 2 Pages: 471-482

    • DOI

      10.1111/cas.13469

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of ADAM10 in satellite cells accelerates muscle regeneration following muscle injury2018

    • Author(s)
      Mizuno Sakiko、Yoda Masaki、Shimoda Masayuki、Chiba Kazuhiro、Nakamura Masaya、Horiuchi Keisuke
    • Journal Title

      Journal of Orthopaedic Research

      Volume: 36 Issue: 8 Pages: 2259-2265

    • DOI

      10.1002/jor.23878

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SOX4, an epithelial-mesenchymal transition inducer, transactivates ADAM28 gene expression and co-localizes with ADAM28 at the invasive front of human breast and lung carcinomas2018

    • Author(s)
      Aya Sasaki, Hitoshi Abe, Satsuki Mochizuki, Masayuki Shimoda and Yasunori Okada
    • Journal Title

      Pathol Int.

      Volume: - Issue: 8 Pages: 449-458

    • DOI

      10.1111/pin.12685

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization Is Up-Regulated and Involved in Hyaluronan Degradation in Human Osteoarthritic Cartilage.2018

    • Author(s)
      Shimizu H, Shimoda M, Mochizuki S, Miyamae Y, Abe H, Chijiiwa M, Yoshida H, Shiozawa J, Ishijima M, Kaneko K, Kanaji A, Nakamura M, Toyama Y, Okada Y.
    • Journal Title

      Am J Pathol.

      Volume: 188 Issue: 9 Pages: 2109-2119

    • DOI

      10.1016/j.ajpath.2018.05.012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Targeted deletion of HYBID (hyaluronan binding protein involved in hyaluronan depolymerization/ KIAA1199/CEMIP) decreases dendritic spine density in the dentate gyrus through hyaluronan accumulation2018

    • Author(s)
      Yoshino Yuta、Shimazawa Masamitsu、Nakamura Shinsuke、Inoue Shintaro、Yoshida Hiroyuki、Shimoda Masayuki、Okada Yasunori、Hara Hideaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 503 Issue: 3 Pages: 1934-1940

    • DOI

      10.1016/j.bbrc.2018.07.138

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective inhibition of ADAM28 suppresses lung carcinoma cell growth and metastasis2018

    • Author(s)
      Satsuki Mochizuki, Masayuki Shimoda, Hitoshi Abe, Yuka Miyamae, Junko Kuramoto, Noriko Aramaki-Hattori, Ken Ishii, Hideki Ueno, Akira Miyakoshi, Kanehisa Kojoh and Yasunoti Okada
    • Journal Title

      Mol. Cancer Ther

      Volume: 17 Issue: 11 Pages: 2427-2438

    • DOI

      10.1158/1535-7163.mct-17-1198

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Isolation of cancer stem cells from human lung carcinoma cell lines by Hoechst side population method.2018

    • Author(s)
      Shimoda M, Ota M, Okada Y
    • Journal Title

      Methods Molec Biol

      Volume: 1692 Pages: 49-59

    • DOI

      10.1007/978-1-4939-7401-6_5

    • ISBN
      9781493974009, 9781493974016
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metalloproteinases in extracellular vesicles.2017

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

      Biochim Biophys Acta Mol Cell Res

      Volume: 1864 Issue: 11 Pages: 1989-2000

    • DOI

      10.1016/j.bbamcr.2017.05.027

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hyaluronan binding protein involved in hyaluronan depolymerization controls endothelial ossification through hyaluronan metabolism.2017

    • Author(s)
      Shimoda M., Yoshida H., Mizuno S., Hirozane T., Horiuchi K., Yoshino Y., Hara H., Kanai Y., Inoue S., Ishijima M. and Okada Y.
    • Journal Title

      Am J Pathol

      Volume: 187 Issue: 5 Pages: 1162-1176

    • DOI

      10.1016/j.ajpath.2017.01.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 腫瘍進展におけるADAM(a disintegrin and metalloproteinase)の役割2018

    • Author(s)
      下田将之
    • Organizer
      第23回日本病態プロテアーゼ学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 内軟骨性骨形成におけるHYBID(hyaluronan-binding protein involved in hyaluronan depolymerization)の機能解析2017

    • Author(s)
      下田将之、吉田浩之、水野早希子、弘實透、堀内圭輔、吉野雄太、原英彰、石島旨章、井上紳太郎、金井 弥栄、岡田保典
    • Organizer
      第30回日本軟骨代謝学会
    • Place of Presentation
      みやこめっせ(京都府京都市)
    • Year and Date
      2017-03-03
    • Related Report
      2016 Research-status Report
  • [Presentation] 組織内微小環境因子代謝を介した腫瘍進展機構に関する研究2017

    • Author(s)
      下田将之
    • Organizer
      第63回日本病理学会秋期特別総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 長管骨形成に関わるHYBID(HYaluronan-Binding protein Involved in hyaluronan Depolymerization)の役割解析2017

    • Author(s)
      下田将之、吉田浩之、水野早希子、弘實透、堀内圭輔、 吉野雄太、原英彰、金井弥栄、井上紳太郎、石島旨章、岡田保典
    • Organizer
      第106回 日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 発育におけるHYBID(HYaluronan-Binding protein Involved in hyaluronan Depolymerization)の機能解析2016

    • Author(s)
      下田将之、吉田浩之、水野早希子、弘實透、堀内圭輔、吉野雄太、原英彰、石島旨章、井上紳太郎、金井弥栄、岡田保典
    • Organizer
      第46回日本創傷治癒学会
    • Place of Presentation
      東京大学内伊藤国際学術研究センター伊藤謝恩ホール・安田講堂(東京都文京区)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
  • [Presentation] HYBID(HYaluronan-Binding protein Involved in hyaluronan Depolymerization)遺伝子欠損マウスの作製と表現型解析2016

    • Author(s)
      下田将之、吉田浩之、水野早希子、弘實透、堀内圭輔、吉野雄太、原英彰、石島旨章、井上紳太郎、金井弥栄、岡田保典
    • Organizer
      第13回日本病理学会カンファレンス
    • Place of Presentation
      六甲山ホテル(兵庫県神戸市)
    • Year and Date
      2016-07-29
    • Related Report
      2016 Research-status Report
  • [Presentation] HYBID(HYaluronan-Binding protein Involved in hyaluronan Depolymerization)遺伝子欠損マウスの作製と表現型解析2016

    • Author(s)
      下田将之、吉田浩之、水野早希子、弘實透、堀内圭輔、井上紳太郎、岡田保典
    • Organizer
      第48回日本結合組織学会学術大会
    • Place of Presentation
      長崎大学医学部良順会館・記念講堂(長崎県長崎市)
    • Year and Date
      2016-06-24
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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