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Finding molecular pathways specific in the highly invasive radioresistant cancer cells and proposing the way to block their invasiveness

Research Project

Project/Area Number 19K08111
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

Fujita Mayumi  国立研究開発法人量子科学技術研究開発機構, 量子生命科学研究所, 主幹研究員 (80580331)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords癌細胞の浸潤 / 癌細胞の転移 / 放射線抵抗性 / 細胞浸潤 / 放射線がん治療 / 浸潤細胞 / 放射線 / 浸潤 / 放射線抵抗性浸潤細胞
Outline of Research at the Start

放射線癌治療をさらに発展させる為には、治療後の再発や浸潤、転移をいかに抑制できるかが重要である。申請者らは、放射線照射は大多数の細胞株の浸潤抑制に効果的であるが、特定の細胞株では放射線照射後に浸潤細胞の数が増加することを明らかにした。中でもPANC-1細胞では、細胞全体の中に「放射線抵抗性浸潤細胞」の集団が存在し、照射後にそれらが選択的に生き残ったために、全体として浸潤細胞の数が上昇していたことが示唆された。では、「放射線抵抗性浸潤細胞」とはどのような細胞なのか? 本研究では、放射線抵抗性浸潤細胞で重要なパスウェイやマーカー分子を調べ、これら細胞集団を効率良く殺傷または抑制する方法を提案する。

Outline of Final Research Achievements

We have recently reported that radiation is effective in reducing the invasion of many cancer cell lines, however, we also confirmed that a minority of cell lines display enhanced invasion following irradiation, including PANC-1. In the case of PANC-1, there were the distinct invading population (INV) within the whole cultured PANC-1 population, which showed resistant to radiation as well as higher metastatic potential, indicated that INV are risk population for cancer treatment. Thus, in this study, we used 7 breast cancer cell lines to further investigate the existence of INV in other cell lines. We found that MDA-MB-468 and SUM149 also include INV population within whole cell population, but of note, their INV were not radio-resistance, indicated that these INV could be killed with radiation. Moreover, we revealed that INV cells have unique character exhibiting hyper-glycolytic phenotype, and thus, inhibitor for glycolysis was effective in blocking their aggressive invasiveness.

Academic Significance and Societal Importance of the Research Achievements

放射線癌治療をさらに発展させる為には、治療後の再発や浸潤、転移をいかに抑制できるかが重要である。我々はPANC-1を用いた研究から、細胞全体の集団の中には一部、顕著に浸潤能が高い「高浸潤細胞」の集団が存在することを明らかにしてきた。さらに細胞株によっては、それら浸潤細胞は放射線にも抵抗性を示すことも見出した。本研究では、このような治療においてリスクとなり得る「高浸潤細胞」で共通する重要因子を調べ、これら細胞集団を効率良く抑制する方法を提案した。この成果は、癌の浸潤・転移抑制剤の開発や、治療後の診断マーカーの開発にも役立つ成果であり、学術的意義や社会的意義が非常に高い結果であると考えている。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (7 results)

All 2022 2021 2020 2019 Other

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

  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Combining Carbon-Ion Irradiation and PARP Inhibitor, Olaparib Efficiently Kills BRCA1-Mutated Triple-Negative Breast Cancer Cells2022

    • Author(s)
      Kawanishi M, Fujita M, Karasawa K
    • Journal Title

      Breast Cancer (Auckl)

      Volume: 16 Pages: 1-11

    • DOI

      10.1177/11782234221080553

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolic characterization of aggressive breast cancer cells exhibiting invasive phenotype: impact of non-cytotoxic doses of 2-DG on diminishing invasiveness2020

    • Author(s)
      Mayumi Fujita, Kaori Imadome, Veena Somasundaram, Miki Kawanishi, Kumiko Karasawa , David A Wink
    • Journal Title

      BMC Cancer

      Volume: 20 Issue: 1 Pages: 929-929

    • DOI

      10.1186/s12885-020-07414-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of nitric oxide in pancreatic cancer cells exhibiting the invasive phenotype2019

    • Author(s)
      Fujita Mayumi、Somasundaram Veena、Basudhar Debashree、Cheng Robert Y.S.、Ridnour Lisa A.、Higuchi Harumi、Imadome Kaori、No Jae Hong、Bharadwaj Gaurav、Wink David A.
    • Journal Title

      Redox Biology

      Volume: 22 Pages: 101158-101158

    • DOI

      10.1016/j.redox.2019.101158

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Role of nitric oxide in pancreatic cancer cells exhibiting the invasive potential2021

    • Author(s)
      Fujita M, Somasundaram V, Basudhar D, Cheng RYS, Ridnour LA, Imadome K, No JH, Bharadwaj G, Wink DA
    • Organizer
      第80回 日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Role of nitric oxide in the invasive pancreatic cancer cells2020

    • Author(s)
      Fujita M, Somasundaram V, Basudhar D, Cheng RYS, Ridnour LA, Imadome K, No JH, Bharadwaj G, Wink DA
    • Organizer
      AACR ANNUAL MEETING 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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