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The mechanism of promoting remote metastasis by exosome derived from pancreatic cancer

Research Project

Project/Area Number 21K08684
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionKobe University

Principal Investigator

Hori Yuichi  神戸大学, 保健学研究科, 教授 (80248004)

Co-Investigator(Kenkyū-buntansha) 清水 一也  神戸大学, 保健学研究科, 保健学研究員 (50335353)
三好 真琴  神戸大学, 保健学研究科, 講師 (50433389)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords膵臓がん / エクソソーム / 遠隔転移 / 転移 / 上皮間葉転換 / 内皮間葉転換 / 膵臓癌
Outline of Research at the Start

研究の概要は膵癌細胞の遠隔転移機構を明らかにして新規治療法を創出することである。我々は正常膵幹細胞やヒト膵癌細胞が幹細胞マーカーCD133を発現することを示した 。また、既存の抗がん剤に耐性の膵癌患者から20種類のCD133陽性膵癌幹細胞株を樹立し、細胞外基質を再構築することで自己複製能を獲得することを示した。また、この細胞株をマウスに移植した腫瘍でも抗がん剤耐性を持つことを示した。本研究では、我々が樹立した①ヒト膵癌幹細胞株と②マウス人工膵癌幹細胞株由来のエクソソームが肝臓や肺で微小環境を構成する機構を解明し、新規治療法を開発する。

Outline of Final Research Achievements

The overall concept of the research is to clarify the mechanism of distant metastasis of pancreatic cancer cells and to create novel therapeutic strategies. Pancreatic cancer has the poorest prognosis among solid tumors, with a 5-year survival rate of less than 10%, and distant metastasis and local invasion determine the prognosis. In this study, we aim to elucidate the molecular mechanism of early distant metastasis by focusing on exosomes secreted by pancreatic cancer cells. We have already established 10 different pancreatic cancer stem cell lines from pancreatic cancer patients resistant to the anticancer drug gemcitabine (GEM). We have also generated mouse engineered pancreatic cancer stem cell lines by transferring oncogenes into CD133-positive mouse pancreatic tissue stem cells. We will elucidate the molecular mechanisms of the early stages of metastasis using exosomes derived from the human and mouse pancreatic cancer stem cell lines we established.

Academic Significance and Societal Importance of the Research Achievements

膵臓がんは臓器別死亡数の第4位にあり、早期診断が困難で予後不良の疾患であり、発見時には多くの症例ですでに遠隔転移や癌性腹膜炎を伴っている。予後を左右する遠隔転移の病態解明や新しい治療法の開発が急務である。最近、がん細胞が細胞間コミュニケーションをはかるツールとして細胞が分泌するエクソソームが注目されている。本研究では、我々が樹立したヒトやマウスの膵臓がん細胞由来のエクソソームが初期の転移にどのように関与するのかを明らかにした。

Report

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

    (18 results)

All 2023 2022 2021

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (15 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Exosomes in ascites from patients with human pancreatic cancer enhance remote metastasis partially through endothelial-mesenchymal transition2023

    • Author(s)
      Kimoto Ai、Kadoi Yusuke、Tsuruda Taisei、Kim Yong-Sik、Miyoshi Makoto、Nomoto Yuna、Nakata Yuna、Miyake Mutsumi、Miyashita Kumiko、Shimizu Kazuya、Ajiki Tetsuo、Hori Yuichi
    • Journal Title

      Pancreatology

      Volume: - Issue: 4 Pages: 377-388

    • DOI

      10.1016/j.pan.2023.04.002

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pancreatic cancer cell-derived exosomes induce epithelial-mesenchymal transition in human pancreatic cancer cells themselves partially via transforming growth factor β12022

    • Author(s)
      Nakayama F , Miyoshi M , Kimoto A , Kawano A, Miyashita K , Kamoshida S , Shimizu K , Hori Y
    • Journal Title

      Med Mol Morphol

      Volume: - Issue: 3 Pages: 227-235

    • DOI

      10.1007/s00795-022-00321-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synbiotics improved stool form via changes in the microbiota and short-chain fatty acids in hemodialysis patients2021

    • Author(s)
      Miyoshi M, Kadoguchi H, Usami M, Hori Y
    • Journal Title

      Kobe J Med Sci

      Volume: 61

    • NAID

      120007185903

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト膵癌患者由来腫瘍片の同所性移植は遠隔転移とがん関連凝固異常を再現できる2023

    • Author(s)
      三宅睦、三好真琴、宮下久美子、中田裕菜、野元優奈、清水一也、堀裕一
    • Organizer
      第54回日本膵臓学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 膵臓がん微小環境構築における免疫担当細胞の関与2023

    • Author(s)
      中田裕菜、三好真琴、宮下久美子、野元優奈、三宅睦、清水一也、堀裕一
    • Organizer
      第54回日本膵臓学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ヒト膵臓がん患者腹水中のエクソソームは内皮間葉転換を介して遠隔転移を促進する2023

    • Author(s)
      野元優奈、三好真琴、宮下久美子、三宅睦、中田裕菜、清水一也、堀裕一
    • Organizer
      第54回日本膵臓学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Monoamine oxidase B inhibitor has anti-tumor effect on gemcitabine-resistant human pancreatic cancer2022

    • Author(s)
      Miyashita K, Miyoshi M, Kimoto A, Ohnaga T, Shimizu K, Hori Y
    • Organizer
      International Association of Pancreatology
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pancreatic cancer cell-derived exosomes induce epithelial mesenchymal transition in human pancreatic cancer cells themselves2022

    • Author(s)
      Miyoshi M, Kimoto A, Ohnaga T, Miyashita K, Shimizu K, Hori Y
    • Organizer
      International Association of Pancreatology
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒト膵癌細胞由来エクソソームは膵癌細胞自身の上皮間葉転換を誘導する2022

    • Author(s)
      木本愛、三好真琴、宮下久美子、大永智貴、清水一也、堀裕一
    • Organizer
      第81回日本癌学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 膵臓がん細胞由来のエクソソームはヒト膵臓がん細胞自身の上皮間葉転換を誘導する2022

    • Author(s)
      木本愛、三好真琴、大永智貴、宮下久美子、後藤百香、三宅睦、中田裕菜、野元優奈、清水一也、堀裕一
    • Organizer
      第54回日本臨床分子形態学会
    • Related Report
      2022 Research-status Report
  • [Presentation] ヒト膵癌患者由来腫瘍片の同所性異種移植モデルは遠隔転移とがん関連凝固異常を再現できる2022

    • Author(s)
      大永智貴、三好真琴、木本愛、宮下久美子、三宅睦、中田裕菜、野元優奈、清水一也、堀裕一
    • Organizer
      第54回日本臨床分子形態学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 膵臓がんの現況と私の膵臓がん研究2022

    • Author(s)
      堀裕一
    • Organizer
      第54回日本臨床分子形態学会
    • Related Report
      2022 Research-status Report
  • [Presentation] PREBIOTICS, PARTIALLY HYDROLYZED GUAR GUM, IMPROVED THE DEFECATION STATUS VIA CHANGES IN THE FECAL MICROBIOTA AND SHORT-CHAIN FATTY ACIDS IN HEMODIALYSIS PATIENTS2022

    • Author(s)
      MIYOSHI M, KADOGUCHI H, USAMI M, HORI Y
    • Organizer
      22nd IUNS-ICN International congress of nutrition in Tokyo
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒト膵癌患者由来腫瘍片の同所性異種移植は遠隔転移とがん関連凝固異常を再現できる2021

    • Author(s)
      大永智貴、渡邊ありさ、三好真琴、宮下久美子、後藤百香、中山郁也、河野朱莉、前谷織江、木本愛、清水一也、堀裕一
    • Organizer
      第30回日本がん転移学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 膵臓がん細胞由来のエクソソームは自身の上皮間葉転換を誘発する2021

    • Author(s)
      木本愛、中山郁也、三好真琴、宮下久美子、後藤百香、河野朱莉、前谷織江、渡邊ありさ、大永智貴、清水一也、堀裕一
    • Organizer
      第52回日本膵臓学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Patient-derived orthotopic pancreatic cancer tissue xenografts recapitulate remote metastasis and cancer-associated hypercoagulation2021

    • Author(s)
      Miyashita K, Miyoshi M, Shimizu K, Kawano A, Hori Y
    • Organizer
      第80回日本癌学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Patient-derived orthotopic pancreatic cancer tissue xenografts recapitulate remote metastasis and cancer-associated hypercoagulation2021

    • Author(s)
      Miyashita K, Miyoshi M, Kimoto A, Ohnaga T, Shimizu K, Hori Y
    • Organizer
      American pancreatic Association 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pancreatic cancer cell-derived exosomes induce their own epithelial-mesenchymal transition2021

    • Author(s)
      Miyoshi M, Miyashita K, Kimoto A, Ohnaga T, Shimizu K, Hori Y
    • Organizer
      American pancreatic Association 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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

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