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Development of bioluminescent sensors and their application to breast cancer cells

Research Project

Project/Area Number 18K19573
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Noda Natsumi  東京大学, 大学院理学系研究科(理学部), 特任研究員 (30624358)

Project Period (FY) 2018-06-29 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords乳癌 / CD44 / 生物発光 / ルシフェラーゼ / 癌幹細胞 / 浸潤 / 発光
Outline of Final Research Achievements

This study aimed to develop new therapy for breast cancer. We focused on CD44, a marker for breast cancer stem cells. CD44 undergoes ectodomain cleavage by membrane-associated metalloproteinases in breast cancer cells. Cleavage plays a critical role in cancer cell migration. To explore inhibitors of CD44 ectodomain cleavage, we developed bioluminescent sensors. The sensors revealed that a drug suppressed the invasion of breast cancer cells.

Academic Significance and Societal Importance of the Research Achievements

現在, 日本において乳癌は40代女性の癌部位別死亡率1位である. トリプルネガティブ(エストロゲン受容体, プロゲステロン受容体, 及びHER2発現陰性)乳癌は, 骨や中枢神経系への転移が多く再発率が高いことから, より優れた治療法の開発が急務である. このような有効な治療法が確立できていない難治性癌に対し, 癌幹細胞を標的とした治療法を開発し, 癌の根治や長期延命を実現したいと考えた. 本研究は, 乳癌幹細胞マーカーであるCD44を標的とした発光センサーを開発し, 乳癌細胞の浸潤を抑制する薬剤を見出すことに成功したことで, 乳癌治療の新たな選択肢となる可能性を示した.

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Development of CD44 bioluminescent sensors to detect the ectodomain cleavage and their application to breast cancer cells2023

    • Author(s)
      野田 なつみ、小澤 岳昌
    • Journal Title

      生化学

      Volume: 95 Issue: 1 Pages: 104-112

    • DOI

      10.14952/SEIKAGAKU.2023.950104

    • ISSN
      0037-1017
    • Year and Date
      2023-02-25
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] スプリットルシフェラーゼアッセイ (用語解説)2023

    • Author(s)
      野田 なつみ、小澤 岳昌
    • Journal Title

      生化学

      Volume: 95 Pages: 117-117

    • Related Report
      2022 Annual Research Report
    • Open Access
  • [Journal Article] Castanospermine suppresses CD44 ectodomain cleavage as revealed by transmembrane bioluminescent sensors2022

    • Author(s)
      Noda Natsumi、Ozawa Takeaki
    • Journal Title

      Journal of Cell Science

      Volume: 135 Issue: 6 Pages: 259314-259314

    • DOI

      10.1242/jcs.259314

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhanced bioluminescent sensor for longitudinal detection of CREB activation in living cells2019

    • Author(s)
      Noda Natsumi、Ishimoto Tetsuya、Mori Hisashi、Ozawa Takeaki
    • Journal Title

      Photochemical & Photobiological Sciences

      Volume: 18 Issue: 11 Pages: 2740-2747

    • DOI

      10.1039/c9pp00249a

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Light-controllable Transcription System by Nucleocytoplasmic Shuttling of a Truncated Phytochrome B2018

    • Author(s)
      Natsumi Noda and Takeaki Ozawa
    • Journal Title

      Photochemistry and Photobiology

      Volume: 94 Issue: 5 Pages: 1071-1076

    • DOI

      10.1111/php.12955

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 乳癌細胞におけるCD44s細胞外ドメイン切断を検出する生物発光センサー2019

    • Author(s)
      野田なつみ、小澤岳昌
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] CREB活性化を検出する生物発光プローブを用いた1細胞イメージング2018

    • Author(s)
      野田なつみ、小澤岳昌
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2024-01-30  

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