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Role of the tumor microenvironment on radiation-induced carcinogenesis

Research Project

Project/Area Number 17K19944
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Health science and related fields
Research InstitutionNational Institute of Public Health

Principal Investigator

Shimura Tsutomu  国立保健医療科学院, その他部局等, 上席主任研究官 (40463799)

Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords放射線発がん / がんの微小環境 / ミトコンドリア / 活性酸素 / がん関連線維芽細胞 / 酸化ストレス / 微小環境 / ROS
Outline of Final Research Achievements

Cancer-associated fibroblasts (CAFs) are an activated from of fibroblasts in tumor tissues. CAF release paracrine factors that promote tumor growth and cancer cell aggressiveness. We investigated the association between oxidative stress and the formation of tumor microenvironments during the development of radiation-related tumors. Reactive Oxygen Species (ROS) play a pivotal role in the process of fibroblasts activation in normal tissue injury. Recovery of damaged cells from radiation is essential for CAF clearance, which restores stromal cell dormancy and prevents tumor microenvironment formation. However, remaining ROS maintained CAF persistence which led to facilitated tumor microenvironment formation. Alterations in stromal cells can contribute to radiation-related tumors. Radiation affects malignant cancer cells directly and indirectly via the tumor stroma.

Academic Significance and Societal Importance of the Research Achievements

放射線被ばくによって将来がんになる不安や子孫への遺伝的影響への懸念など被ばくによる精神的ストレスが原因となる二次的な健康影響が問題となっている。放射線による健康影響について、継続して適切な情報を発信することが重要である。本研究の成果は、福島事故後に問題となっている低線量放射線発がんの機序解明の一端となり得るものである。我々は、放射線発がんには、単にがん細胞の遺伝子変異の蓄積だけでなく、がん微小環境の形成が重要であると考える。本申請研究の成果により、放射線発がんリスク評価の根拠となる科学的知見の蓄積が期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Epicatechin as a Promising Agent to Countermeasure Radiation Exposure by Mitigating Mitochondrial Damage in Human Fibroblasts and Mouse Hematopoietic Cells2019

    • Author(s)
      1) Tsutomu Shimura, Mao Koyama, Daiki Aono, Naoki Kunugita
    • Journal Title

      The FASEB J

      Volume: in press Issue: 6 Pages: 6867-6876

    • DOI

      10.1096/fj.201802246rr

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation-Induced Myofibroblasts Promote Tumor Growth via Mitochondrial ROS-Activated TGFβ Signaling.2018

    • Author(s)
      Shimura T, Sasatani M, Kawai H, Kamiya K, Kobayashi J, Komatsu K, Kunugita N
    • Journal Title

      Mol. Cancer Res.

      Volume: 16(11) Issue: 11 Pages: 1676-1686

    • DOI

      10.1158/1541-7786.mcr-18-0321

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of DNA-generated gold nanoparticles to radiosensitize and eradicate radioresistant glioma stem cells2018

    • Author(s)
      Kunoh T, Shimura T, Kasai T, Matsumoto S, Mahmud H, Khayrani A, Seno M, Kunoh H, Takada J.
    • Journal Title

      Nanotechnology

      Volume: 30 Issue: 5 Pages: 055101-055101

    • DOI

      10.1088/1361-6528/aaedd5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tokyo Electric Power Company Fukushima Dai-ichi Nuclear Power Plant accident and public health.2018

    • Author(s)
      Kunugita Naoki, Shimura Tsutomu, Terada Hiroshi, Yamaguchi Ichiro.
    • Journal Title

      Journal of the National Institute of Public Health

      Volume: 67 Pages: 2-10

    • NAID

      130006706916

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation values and current situation of radioactive materials in food.2018

    • Author(s)
      Terada Hiroshi, Yamaguchi Ichiro, Shimura Tsutomu, Svendsen Erik.R., Kunugita Naoki.
    • Journal Title

      Journal of the National Institute of Public Health

      Volume: 67 Pages: 21-33

    • NAID

      130006706913

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lessons learned from radiation risk communication activities regarding the Fukushima nuclear accident.2018

    • Author(s)
      Yamaguchi Ichiro, Shimura Tsutomu, Terada Hiroshi, Svendsen Erik.R., Kunugita Naoki
    • Journal Title

      Journal of the National Institute of Public Health

      Volume: 67 Pages: 93-102

    • NAID

      130006706928

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lessons learned from radiation biology: Health effects of low levels of exposure to ionizing radiation on humans regarding the Fukushima accident.2018

    • Author(s)
      Shimura Tsutomu, Yamaguchi Ichiro, Terada Hiroshi, Kunugita Naoki.
    • Journal Title

      Journal of the National Institute of Public Health

      Volume: 67 Pages: 115-122

    • NAID

      130006706963

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] ATM-mediated mitochondrial damage response triggered by nuclear DNA damage in normal human lung fibroblasts.2017

    • Author(s)
      Shimura T, Sasatani M, Kawai H, Kamiya K, Kobayashi J, Komatsu K, Kunugita N.
    • Journal Title

      Cell Cycle.

      Volume: 16(24) Issue: 24 Pages: 2345-2354

    • DOI

      10.1080/15384101.2017.1387697

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of Rev1 promotes the development of carcinogen-induced intestinal adenomas via accumulation of point mutation and suppression of apoptosis proportionally to the Rev1 expression level.2017

    • Author(s)
      Sasatani M, Xi Y, Kajimura J, Kawamura T, Piao J, Masuda Y, Honda H, Kubo K, Mikamoto T, Watanabe H, Xu Y, Kawai H, Shimura T, Noda A, Hamasaki K, Kusunoki Y, Zaharieva EK, Kamiya K.
    • Journal Title

      Carcinogenesis.

      Volume: 38(5) Issue: 5 Pages: 570-578

    • DOI

      10.1093/carcin/bgw208

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ミトコンドリアの放射線応答と放射線発がんへの影響2017

    • Author(s)
      志村勉、欅田尚樹
    • Journal Title

      放射線生物研究

      Volume: 52 Pages: 183-193

    • NAID

      40021257662

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Targeting the AKT/cyclin D1 pathway to overcome intrinsic and acquired radioresistance of tumors for effective radiotherapy2016

    • Author(s)
      Shimura T
    • Journal Title

      Int J Radiat Biol.

      Volume: 93 Issue: 4 Pages: 381-385

    • DOI

      10.1080/09553002.2016.1257832

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells.2019

    • Author(s)
      Shimura T , Koyama M, Aono D, Kunugita N.
    • Organizer
      日本放射線影響学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 放射線誘発がん関連線維芽細胞は、活性酸素によるTGFbeta;シグナリング経路の活性化を介してがんの増殖を促進する2018

    • Author(s)
      志村勉、笹谷めぐみ、河合秀彦、神谷研二、小林純也、小松賢志、欅田尚樹
    • Organizer
      第61回日本放射線影響学会,
    • Related Report
      2018 Research-status Report
  • [Presentation] Radiation-induced mitochondrial damage in neural progenitor stem cells and differentiated cells.2018

    • Author(s)
      Shimura Tsutomu and Kunugita Naoki
    • Organizer
      The 8th Annual Meeting of the International Society of Radiation Neurobiology.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A comparison of radiation-induced mitochondrial damage between neural progenitor stem cells and differentiated cells.2017

    • Author(s)
      Shimura Tsutomu, Sasatani Megumi, Kawai Hidehiko, Kamiya Kenji, Kunugita Naoki.
    • Organizer
      The 1st international symposium of the network-type joint usage/research center for radiation disaster medical science.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ATMが制御する核とミトコンドリアの放射線応答2017

    • Author(s)
      志村勉、笹谷めぐみ、河合秀彦、神谷研二、小林純也、小松賢志、欅田尚樹
    • Organizer
      第60回日本放射線影響学会
    • Related Report
      2017 Research-status Report
  • [Book] Encyclopedia of Environmental Health, 2nd Edition.2019

    • Author(s)
      Shimura T, Yamaguchi I. Kunugita N.
    • Total Pages
      4884
    • Publisher
      ELSEVIER
    • ISBN
      9780444639516
    • Related Report
      2019 Annual Research Report

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Published: 2017-07-21   Modified: 2021-02-19  

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