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Development of innovative cancer diagnostic and therapeutic seeds focusing on tissue specific exosomics using xenotransplantation model

Research Project

Project/Area Number 18H04064
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionKyoto University

Principal Investigator

Ogawa Osamu  京都大学, 医学研究科, 名誉教授 (90260611)

Co-Investigator(Kenkyū-buntansha) 赤松 秀輔  京都大学, 医学研究科, 准教授 (20767248)
山崎 俊成  京都大学, 医学研究科, 講師 (00607749)
齊藤 亮一  京都大学, 医学研究科, 助教 (30792270)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000)
Fiscal Year 2021: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2020: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2019: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2018: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Keywordsエクソソーム / 患者癌組織由来ゼノグラフト / 腎細胞癌 / 薬剤抵抗性 / 転移形成 / 前転移ニッチ / 腫瘍間質相互作用 / 泌尿器 / 癌 / 患者組織由来ゼノグラフト
Outline of Final Research Achievements

Intercellular communication between cancer cells and stromal cells is essential for drug resistance and metastasis formation of cancer, exosomes play a important role as messenger. In our study of drug resistance, exosomes secreted from sunitinib-resistant tumor have shown distinct miRNA profiles compared with control. Further study is required to elucidate the mechanism by which exosomes induce drug resistance. In our study of metastasis formation, we established a bone metastatic RCC cell line. Treatment of mice with exosomes collected from culture supernatant of bone metastatic RCC cells promoted angiogenesis in bone in a time-dependent manner and increased bone metastasis. We showed that exosomal CD13 contributed to angiogenesis. In addition, exosomes from bone metastatic RCC contained abundant CD13 and promoted angiogenesis compared with exosomes from RCC without metastasis. Our findings provide a new insight to the role of exosome in cancer metastasis and drug resistance.

Academic Significance and Societal Importance of the Research Achievements

本研究により、エクソソームが時間依存性に腎癌骨転移の前転移ニッチを形成することが示された。また薬剤抵抗性腫瘍でエクソソーム中のmiRNAプロファイルは異なり、癌の薬剤抵抗性や転移形成の腫瘍間質相互作用にエクソソームが関わっていることが示唆された。
今回の研究成果により、転移や薬剤抵抗性機序の解明につながるのみならず、エクソソームを転移予測のバイオマーカーに用いたり、治療抵抗性克服の治療ターゲットとするなど、臨床応用につながることが期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (10 results)

All 2021 2020

All Presentation (10 results) (of which Int'l Joint Research: 3 results)

  • [Presentation] Extracellular Vesicles(EVs) secreted from bone metastatic RCC cells induce angiogenesis in bone marrow and facilitated bone metastasis.2021

    • Author(s)
      武田将司
    • Organizer
      AUA2021 Annual Meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Extracellular Vesicles secreted by bone tropic renal cell carcinoma induce angiogenesis in bone marrow with potential to facilitate bone metastasis2021

    • Author(s)
      武田将司
    • Organizer
      ISEV 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Extracellular vesicles secreted by bone tropic renal cell carcinoma induce angiogenesis in bone marrow with potential to facilitate bone metastasis2021

    • Author(s)
      武田将司
    • Organizer
      第73回西日本泌尿器科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨転移指向性腎癌細胞株は分泌する細胞外小胞は骨髄の血管新生を誘導し骨転移を促進する2021

    • Author(s)
      武田将司
    • Organizer
      第109回日本泌尿器科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨転移指向性腎癌細胞株由来のエクソソームは骨髄血管の増生、拡張を誘導する2021

    • Author(s)
      武田 将司
    • Organizer
      第30回泌尿器科分子・細胞研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 骨転移指向性腎癌細胞株由来エクソソームは骨髄において血管増生を誘導する2020

    • Author(s)
      武田 将司
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Bone tropic renal cell carcinoma cell lines-derived exosomes induce blood vessel formation in bone marrow2020

    • Author(s)
      武田 将司
    • Organizer
      18th Urological Association of Asia (UAA) Congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tumor exosomes derived from bone tropic renal cell carcinoma cell lines induce microvascular dilation in bone marrow2020

    • Author(s)
      武田 将司
    • Organizer
      第7回日本細胞外小胞学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] スニチニブ抵抗性の腎癌ゼノグラフト腫瘍から分離したexosomal miRNAの解析2020

    • Author(s)
      武田 将司
    • Organizer
      第108回日本泌尿器学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 第108回日本泌尿器科学会総会2020

    • Author(s)
      武田 将司
    • Organizer
      スニチニブ抵抗性の腎癌ゼノグラフト腫瘍から分離したexosomal miRNAの解析
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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