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Development of Diagnostic System in Bone and Soft Tissue Sarcoma Targeting Tumor Derived Exosome

Research Project

Project/Area Number 19K18466
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionOkayama University (2019, 2021-2022)
National Cancer Center Japan (2020)

Principal Investigator

YOKOO Suguru  岡山大学, 医学部, 客員研究員 (00781204)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsリキッドバイオプシー / 液体生検 / 滑膜肉腫 / MCT1 / バイオマーカー / 骨軟部肉腫 / 軟部肉腫 / 体液診断 / エクソソーム
Outline of Research at the Start

腫瘍分泌エクソソームを標的とした血中バイオマーカーの探索を目的としている。特異的な融合遺伝子の発見により骨軟部肉腫における診断に大きな進展がみられたように、肉腫特異的分子の特定により早期発見だけでなくモニタリングに使用できることが期待される。当研究施設では以前から骨肉腫や粘液型線維肉腫、滑膜肉腫などの研究・発表を行っており、これらの肉腫を中心に特異的分子の特定を行う予定である。そして脂肪肉腫など骨軟部肉腫において頻度の高い肉腫に加え、明細胞肉腫など特異的な融合遺伝子が発見されているがモニタリングが困難である様々な組織型も網羅していく。

Outline of Final Research Achievements

In this study, we identified monocarboxylate transporter 1 (MCT1), a protein present on the membrane surface of extracellular vesicles derived from synovial sarcoma (SS).
MCT1 was highly expressed in extracellular vesicles from SS patients, SS cell lines, and SS xenograft mouse. The expression of MCT1 in SS patients was decreased after treatment compared to before treatment. Furthermore, suppression of MCT1 in SS cell lines reduced tumor proliferation, migration, and invasion. MCT1 expression in cytoplasm and/or membrane of SS was associated with poor prognosis.
MCT1 labeling in SS can be a marker for early diagnosis and recurrence. It was also suggested that suppressing MCT1 has a potential in the treatment of SS.

Academic Significance and Societal Importance of the Research Achievements

予後不良の骨軟部肉腫の一つである滑膜肉腫におけるMCT1標識により早期診断や再発のマーカーとなり得る。またMCT1を抑制することで、滑膜肉腫の治療に役立つ可能性も示唆された。

Report

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

    (9 results)

All 2023 2022 2021 2020 2019

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

  • [Journal Article] Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma2021

    • Author(s)
      Yokoo Suguru、Fujiwara Tomohiro、Yoshida Aki、Uotani Koji、Morita Takuya、Kiyono Masahiro、Hasei Joe、Nakata Eiji、Kunisada Toshiyuki、Iwata Shintaro、Yonemoto Tsukasa、Ueda Koji、Ozaki Toshifumi
    • Journal Title

      Cancers

      Volume: 13 Issue: 8 Pages: 1823-1823

    • DOI

      10.3390/cancers13081823

    • NAID

      120007037389

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma2020

    • Author(s)
      Takuya Morita, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Toshiyuki Kunisada, Toshifumi Ozaki
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1 Pages: 9414-9414

    • DOI

      10.1038/s41598-020-66120-8

    • NAID

      120006883488

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Circulating CSF-1 predicts infiltration of tumor-associated macrophage and prognosis in patients with myxofibrosarcoma and undifferentiated sarcoma2023

    • Author(s)
      Toshiaki Hata
    • Organizer
      Orthopaedic Research Society ORS 2023 Annual Meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Circulating cytokines as a blood-based biomarker predictive of TAM infiltration and prognosis in patients with infiltrative soft-tissue sarcomas2022

    • Author(s)
      畑利彰
    • Organizer
      日本癌学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 腫瘍随伴マクロファージの浸潤及び予後を予測する血中バイオマーカーの特定:浸潤性軟部肉腫における検討2022

    • Author(s)
      畑利彰
    • Organizer
      日本整形外科学会基礎学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Antitumor effect of CSF-1/CSF-1R blockade in soft-tissue sarcomas2022

    • Author(s)
      近藤彩奈
    • Organizer
      日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 軟部肉腫に対する抗 CSF-1R 阻害薬の有効性:抗腫瘍効果と微小環境へ与える影響2022

    • Author(s)
      近藤彩奈
    • Organizer
      日本整形外科学会基礎学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Establishment of Liquid Biopsy Targeting Exosomes Derived from Synovial Sarcoma2020

    • Author(s)
      Yokoo Suguru, Tomohiro Fujiwara, Koji Uotani, Aki Yoshida, Takuya Morita, Masahiro Kiyono, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki
    • Organizer
      Orthopaedic Research Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腫瘍由来エクソソームを標的とした滑膜肉腫におけるリキッドバイオプシーの開発2019

    • Author(s)
      横尾賢、藤原 智洋、吉田 晶、清野 正普、望月 雄介、出宮 光二、上甲 良二、久禮 美穂、尾崎 敏文
    • Organizer
      第34回 日本整形外科学会基礎学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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