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Pancreatic cancer derived exosomes promote early liver metastasis

Research Project

Project/Area Number 18K08705
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, 助教 (50433389)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥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 / 肝転移 / 膵癌 / 膵臓癌
Outline of Final Research Achievements

Pancreatic cancer is the fourth leading cause of cancer mortality in Japan, and distant metastasis is a major prognostic factor. Recently, it has been revealed that all cells secrete tiny extracellular vesicles called exosomes for intercellular communication, and various reports have been published on cancer cells. In this study, we were able to reconstruct pre-metastatic niche in the liver using exosomes derived from (1) a human pancreatic cancer stem cell line that we established and (2) a mouse artificial pancreatic cancer stem cell line generated by oncogene transfer to pancreatic-tissue specific stem cells. The metastatic mechanism such as epithelial-mesenchymal transition was also elucidated at the molecular level. The results of this research will lead to the development of therapeutic drugs targeting exosomes and contribute to the improvement of the prognosis of pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

手術、抗がん剤、放射線治療の進歩にもかかわらず、膵臓癌の5年生存率は未だ10%以下で、固形癌の中で最も予後不良と言われる。今後も罹患数や死亡数は増加すると世界中で予測されており、肝臓や肺などへの転移や神経浸潤といった膵臓癌に特徴的な病態の解明やその対策が待たれる。本研究では、膵臓癌の転移機構を明らかにするため、膵臓癌が分泌するエクソソームと呼ばれる微小な小胞に着目して実験を行った。その結果、エクソソーム投与により、転移のプロセスが亢進することが判明した。この成果はエクソソームを標的とした治療薬の開発に繋がり、膵臓癌の予後改善に貢献できる。

Report

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

    (27 results)

All 2022 2021 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (23 results) (of which Int'l Joint Research: 3 results)

  • [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 Annual Research 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: 2021

    • NAID

      120007185903

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prebiotics improved the defecation status via changes and short-chain fatty acids in hemodialysis patients.2020

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

      Kobe J Med Sci.

      Volume: 66

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Xenografts Derived From Patients? Ascites Recapitulate the Gemcitabine Resistance Observed in Pancreatic Cancer Patients2019

    • Author(s)
      Machinaga Akihito、Hori Yuichi、Shimizu Kazuya、Okahara Kyohei、Yanagita Emmy、Miyoshi Makoto、Itoh Tomoo、Sasai Ken
    • Journal Title

      Pancreas

      Volume: 48 Issue: 10 Pages: 1294-1302

    • DOI

      10.1097/mpa.0000000000001438

    • NAID

      120006777076

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵臓がん細胞由来エクソソームは血管内皮細胞を傷害して遠隔転移を亢進する2021

    • Author(s)
      堀裕一、清水一也、三好真琴、寺田夢、脇田美音、大下彩、高嶋宏滋、宮下久美子、後藤百香、中山郁也、河野朱莉、前谷織江、渡邊ありさ、味木徹夫
    • Organizer
      第51回日本膵臓学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒト膵臓がんorthotopic allograft implantationマウスモデルの開発2021

    • Author(s)
      渡邊ありさ、清水一也、三好真琴、寺田夢、脇田美音、大下彩、高嶋宏滋、宮下久美子、後藤百香、中山郁也、河野朱莉、前谷織江、味木徹夫、堀裕一
    • Organizer
      第51回日本膵臓学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 膵臓がん細胞由来エクソソームは血管内皮細胞を傷害して遠隔転移を亢進する2020

    • Author(s)
      後藤百香、清水一也、三好真琴、寺田夢、脇田美音、大下彩、高嶋宏滋、宮下久美子、渡邊ありさ、中山郁也、河野朱莉、前谷織江、堀裕一
    • Organizer
      第29回日本がん転移学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒト膵臓がんorthotopic allograft implantationマウスモデルの開発2020

    • Author(s)
      前谷織江、清水一也、三好真琴、寺田夢、脇田美音、大下彩、高嶋宏滋、宮下久美子、渡邊ありさ、後藤百香、中山郁也、河野朱莉、堀裕一
    • Organizer
      第29回日本がん転移学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Exosomes from pancreatic cancer cells promote distant metastasis due to injured vascular endothelial cells2020

    • Author(s)
      Akari Kawano, Kazuya Shimizu, Makoto Miyoshi, Kumiko Miyashita, Yume Terada, Mion Wakita, Aya Oshimo, Hiroshi Takashima, Yuichi Hori
    • Organizer
      第79回日本癌学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒト膵臓がん細胞のorthotopic allograft implantationマウスモデルの開発2020

    • Author(s)
      中山郁也、清水一也、三好真琴、寺田夢、脇田美音、大下彩、高嶋宏滋、宮下久美子、渡邊ありさ、後藤百香、河野朱莉、前谷織江、味木徹夫、堀裕一
    • Organizer
      JDDW2020
    • Related Report
      2020 Research-status Report
  • [Presentation] 膵臓がん細胞由来エクソソームは血管内皮細胞を傷害して遠隔転移を亢進する2020

    • Author(s)
      後藤百香、三好真琴、清水一也、宮下久美子、前谷織江、堀裕一
    • Organizer
      第43回日本分子生物学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒト膵臓がん同所性移植片移植マウスモデルの開発2020

    • Author(s)
      前谷織江、三好真琴、清水一也、宮下久美子、後藤百香、堀裕一
    • Organizer
      第43回日本分子生物学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Monoamine oxidase B inhibitor has anti-proliferative effect on Gemcitabine-resistant pancreatic cancer cells2020

    • Author(s)
      Kumiko Miyashita, Makoto Miyoshi, Kazuya Shimizu, Ken Sasai, Tsuyoshi Akagi, Yuichi Hori
    • Organizer
      第43回日本分子生物学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒト膵癌細胞由来エクソソームは肝転移を亢進する2019

    • Author(s)
      高嶋宏滋、清水一也、鶴田大生、梅本陵平、寺田夢、脇田美音、大下彩、三好真琴、味木徹夫、堀裕一
    • Organizer
      第50回日本膵臓学会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト膵癌細胞由来エクソソームは遠隔転移を亢進する2019

    • Author(s)
      寺田夢、清水一也、鶴田大生、梅本陵平、脇田美音、大下彩、高嶋宏滋、宮下久美子、三好真琴、堀裕一
    • Organizer
      第78回日本癌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト膵癌細胞由来エクソソームは肝転移を亢進する2019

    • Author(s)
      大下彩、清水一也、鶴田大生、梅本陵平、寺田夢、高嶋宏滋、脇田美音、宮下久美子、三好真琴、堀裕一
    • Organizer
      第27回JDDW
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト膵癌細胞由来エクソソームは肝転移を亢進する2019

    • Author(s)
      脇田美音、清水一也、鶴田大生、梅本陵平、寺田夢、大下彩、高嶋宏滋、宮下久美子、三好真琴、堀裕一
    • Organizer
      第28回日本がん転移学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗がん剤耐性の膵臓癌に対する脂質メディエーターの効果2019

    • Author(s)
      梅本陵平、清水一也、鶴田大生、大下彩、高嶋宏滋、寺田夢、脇田美音、 三好真琴、堀裕一
    • Organizer
      第51回日本臨床分子形態学会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト膵癌細胞由来エクソソームは遠隔転移を亢進する2019

    • Author(s)
      鶴田大生、清水一也、梅本陵平、大下彩、寺田夢、高嶋宏滋、脇田美音、宮下久美子、三好真琴、堀裕一
    • Organizer
      第51回日本臨床分子形態学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗がん剤Gemcitabine耐性マウス膵癌細胞の樹立とその解析2018

    • Author(s)
      鶴田大生、清水一也、梅本陵平、角井祐介、竹垣普恵、西村綾乃、三好真琴、赤城剛、笹井研、堀裕一
    • Organizer
      第49回日本膵臓学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 抗がん剤Gemcitabine耐性マウス膵癌細胞の樹立とその解析2018

    • Author(s)
      梅本陵平、清水一也、鶴田大生、角井祐介、竹垣普恵、西村綾乃、三好真琴、堀裕一
    • Organizer
      第50回日本臨床分子形態学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Ascites-derived PDX models effectively recapitulate the gemcitabine-resistance observed in pancreatic cancer patients.2018

    • Author(s)
      Akihito Machinaga, Yuichi Hori, Kazuya Shimizu, Kyohei Okahara, Makoto miyoshi, Tomoo Itho, Ken Sasai
    • Organizer
      AACR special conference on Pancreatic Cancer: Advances in Science and Clinical Care
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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

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