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Novel method for diagnosis and therapy of bladder cancer by targeting urinary CD55/CD9 double-positive exosomes

Research Project

Project/Area Number 21K09384
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Kikuchi Eiji  聖マリアンナ医科大学, 医学部, 教授 (10286552)

Co-Investigator(Kenkyū-buntansha) 吉岡 祐亮 (吉岡祐亮)  東京医科大学, 医学部, 講師(特任) (60721503)
薄場 渉  聖マリアンナ医科大学, 医学部, 助教 (90867649)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords膀胱癌 / エクソソーム / CD55 / ExoScreen / バイオマーカー / 膀胱腔内注入療法
Outline of Research at the Start

再発・病期進展の可能性が高い筋層非浸潤性膀胱癌に対する新たなバイオマーカーを用いた診断方法ならびに治療法の開発を目的に、膀胱癌から分泌されるCD55およびCD9を膜タンパクとして持つエクソソーム(CD55+9+exosome)を指標として、膀胱癌を早期診断する感度と特異度に優れた方法を発案した。本研究では尿中のCD55+9+exosomeが、膀胱癌の診断・予後マーカーとして有用であることを検証し、膀胱癌の機能との関連性を解明する。さらに、CD55+9+exosomeの分泌を抑制するmiRNAを見出し、膀胱癌の機能に与える影響を解析し、このmiRNAを用いた新規膀胱腔内注入療法の開発を目指す。

Outline of Final Research Achievements

The purpose of this study is to validate the usefulness of urinary CD55+9+exosome, which is upregulated in bladder cancer patients, as a diagnostic and prognostic marker for bladder cancer, and to elucidate the role of CD55+9+exosome in the tumor environment of bladder cancer patients. Quantification of urinary CD55+9+exosomes using the ExoScreen method proved to be a very useful diagnostic method for bladder cancer. Urinary CD55+9+exosome levels were associated with bladder cancer grade and invasion, suggesting that they may be prognostic markers for recurrence and stage progression. Cisplatin exposure was found to increase CD55+9+exosome secretion in bladder cancer cell lines. This indicates that CD55+9+exosome may also contribute to resistance to anticancer drugs.

Academic Significance and Societal Importance of the Research Achievements

従来検討されてきた尿中の膀胱腫瘍マーカーは感度、特異度や尿中安定性に問題があるが、CD55+9+exosomeはそれらの問題をクリアできる可能性を持つ。さらに、今回尿中CD55+9+exosomeの定量は膀胱癌の診断法として有用であることが示され、即時に臨床応用が可能なExoScreen法を用いることで、新たな診断法開発の早期実現が期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (4 results)

All 2023 2022

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

  • [Journal Article] High‐grade bladder cancer cells secrete extracellular vesicles containing miRNA‐146a‐5p and promotes angiogenesis2022

    • Author(s)
      Prieto‐Vila Marta、Usuba Wataru、Yoshioka Yusuke、Takeshita Fumitaka、Yoshiike Miki、Sasaki Hideo、Yamamoto Yusuke、Kikuchi Eiji、Ochiya Takahiro
    • Journal Title

      Journal of Extracellular Biology

      Volume: 1 Issue: 8

    • DOI

      10.1002/jex2.47

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 尿中CD55/CD9共陽性エクソソームは膀胱癌の新規診断バイオマーカーかつ予後進展に関与する2023

    • Author(s)
      薄場渉, 吉池美紀, 荒武里衣, 吉岡祐亮, 山田龍治, 早川望, 落谷孝広, 菊地栄次
    • Organizer
      第110回日本泌尿器科学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 膀胱がんにおける尿中エクソソームの表面抗原CD55・CD9と内包物質miR-146a-5pのバイオマーカーとしての検討.2023

    • Author(s)
      薄場渉, 吉池美紀, 荒武里衣, 吉岡祐亮, 山田龍治, 早川望, 落谷孝弘, 菊地栄次.
    • Organizer
      第32回泌尿器科分子・細胞研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] CD55 positive exosomes as a novel urinary biomarker for bladder cancer.2022

    • Author(s)
      Hayakawa Nozomi, Yamada Ryuji, Aratake Satoe, Yoshiike Miki, Usuba Wataru, Yoshioka Yusuke, Ochiya Takahiro, Kikuchi Eiji.
    • Organizer
      19th Urological Association of Asia Congress
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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