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Impact of intraperitoneal tumor microenvironment on peritoneal dissemination of gastric cancer via involvement of extracellular vesicles

Research Project

Project/Area Number 18K08679
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 InstitutionOkayama University

Principal Investigator

Kagawa Shunsuke  岡山大学, 大学病院, 准教授 (00362971)

Co-Investigator(Kenkyū-buntansha) 吉田 龍一  岡山大学, 大学病院, 助教 (80534768)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords胃癌 / 腹膜播種 / 細胞外小胞体 / 腫瘍微小環境 / 腫瘍関連マクロファージ / 癌微小環境 / マクロファージ / IL-6
Outline of Final Research Achievements

Macrophages promoting tumor progression are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination. In this study, we investigated the effect of gastric cancer-derived extracellular vesicles (EVs) on the mechanism by which macrophages differentiate into tumor-promoting forms. EV was extracted from ascites of the gastric cancer patient and culture supernatant of the gastric cancer cell. Their purified EVs induced differentiation into tumor-promoting macrophages when applied to peripheral blood mononuclear cells. Macrophages differentiated with gastric cancer-derived EVs promoted the migration of gastric cancer cells, and these EVs possessed STAT3 protein. These results suggest that gastric carcinoma-derived EVs can affect macrophage differentiation and are factors that form the peritoneal environment to promote tumors.

Academic Significance and Societal Importance of the Research Achievements

治療法の進歩にもかかわらず、胃癌の腹膜播種は今なお極めて難治である。新たな治療戦略の開発のために新たな病態の解明が求められている。その病態の新たな側面を解明するため、本研究では腹腔内環境に着目して解析した。我々の研究では胃癌患者の腹腔内に存在している細胞外小胞体が、マクロファージに作用し、腫瘍を促進する腹腔内環境の形成に加担していることを示すことができ、胃癌腹膜播種の病態解明につながる新しい知見が得られた。

Report

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

    (16 results)

All 2021 2020 2019 2018

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Extracellular vesicles shed from gastric cancer mediate protumor macrophage differentiation2021

    • Author(s)
      Ito Atene、Kagawa Shunsuke、Sakamoto Shuichi、Kuwada Kazuya、Kajioka Hiroki、Yoshimoto Masashi、Kikuchi Satoru、Kuroda Shinji、Yoshida Ryuichi、Tazawa Hiroshi、Fujiwara Toshiyoshi
    • Journal Title

      BMC Cancer

      Volume: 21 Issue: 1 Pages: 102-114

    • DOI

      10.1186/s12885-021-07816-6

    • NAID

      120006980466

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis2021

    • Author(s)
      Kajioka Hiroki、Kagawa Shunsuke、Ito Atene、Yoshimoto Masashi、Sakamoto Shuichi、Kikuchi Satoru、Kuroda Shinji、Yoshida Ryuichi、Umeda Yuzo、Noma Kazuhiro、Tazawa Hiroshi、Fujiwara Toshiyoshi
    • Journal Title

      Cancer Letters

      Volume: 497 Pages: 1-13

    • DOI

      10.1016/j.canlet.2020.10.015

    • NAID

      120007188794

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Impact of Sarcopenia on Gastric Cancer.2019

    • Author(s)
      Kuwada K, Kuroda S, Kikuchi S, Yoshida R, Nishizaki M, Kagawa S, Fujiwara T.
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 5 Pages: 2241-2249

    • DOI

      10.21873/anticanres.13340

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endoscopic Ultrasound-Guided Transgastric Drainage of an IntraAbdominal Abscess following Gastrectomy.2019

    • Author(s)
      Kikuchi S, Kubota T, Kuroda S, Nishizaki M, Kagawa S, Kato H, Okada H, Fujiwara T.
    • Journal Title

      Clinical endoscopy

      Volume: 52 Issue: 4 Pages: 373-376

    • DOI

      10.5946/ce.2018.134

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of the Effects of Epidural Analgesia and Patient-controlled Intravenous Analgesia on Postoperative Pain Relief and Recovery After Laparoscopic Gastrectomy for Gastric Cancer.2019

    • Author(s)
      Kikuchi S, Kuroda S, Nishizaki M, Matsusaki T, Kuwada K, Kimura Y, Kagawa S, Morimatsu H, Fujiwara T.
    • Journal Title

      Surgical laparoscopy, endoscopy & percutaneous techniques

      Volume: 29 Issue: 5 Pages: 405-408

    • DOI

      10.1097/sle.0000000000000605

    • Related Report
      2019 Research-status Report
  • [Journal Article] Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer.2019

    • Author(s)
      Sakamoto S, Kagawa S, Kuwada K, Ito A, Kajioka H, Kakiuchi Y, Watanabe M, Kagawa T, Yoshida R, Kikuchi S, Kuroda S, Tazawa H, Fujiwara T.
    • Journal Title

      Oncoimmunology

      Volume: 8 Issue: 12 Pages: e1671760-e1671760

    • DOI

      10.1080/2162402x.2019.1671760

    • NAID

      120006767321

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment?colorectal cancer network2019

    • Author(s)
      Ieda Takeshi、Tazawa Hiroshi、Okabayashi Hiroki、Yano Shuya、Shigeyasu Kunitoshi、Kuroda Shinji、Ohara Toshiaki、Noma Kazuhiro、Kishimoto Hiroyuki、Nishizaki Masahiko、Kagawa Shunsuke、Shirakawa Yasuhiro、Saitou Takashi、Imamura Takeshi、Fujiwara Toshiyoshi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 16378-16378

    • DOI

      10.1038/s41598-019-52816-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer2018

    • Author(s)
      Kuwada Kazuya、Kagawa Shunsuke、Yoshida Ryuichi、Sakamoto Shuichi、Ito Atene、Watanabe Megumi、Ieda Takeshi、Kuroda Shinji、Kikuchi Satoru、Tazawa Hiroshi、Fujiwara Toshiyoshi
    • Journal Title

      Journal of Experimental & Clinical Cancer Research

      Volume: 37 Issue: 1 Pages: 307-307

    • DOI

      10.1186/s13046-018-0981-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer.2018

    • Author(s)
      Watanabe M, Kagawa S, Kuwada K, Hashimoto Y, Shigeyasu K, Ishida M, Sakamoto S, Ito A, Kikuchi S, Kuroda S, Kishimoto H, Tomida S, Yoshida R, Tazawa H, Urata Y, Fujiwara T
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 10 Pages: 3263-3271

    • DOI

      10.1111/cas.13760

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 好中球細胞外トラップはHMGB1 を介して膵癌にEMT を誘導し,肝転移を助長する2020

    • Author(s)
      梶岡裕紀、香川俊輔、田澤大、國土泰孝、村岡篤、藤原俊義
    • Organizer
      第120回日本外科学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 好中球と血小板の相互作用が胆管癌の悪性形質転換を促進する2020

    • Author(s)
      吉本匡志、香川俊輔、梶原義典、西山岳芳、李云成、岡林弘樹、菊地覚次、黒田新士、田澤大、藤原俊義
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The reciprocal interaction between neutrophil extracellular traps and cancer cells impact on their malignant potentials2019

    • Author(s)
      H. Kajioka, S. Kagawa, A. ito, K. Kuwada, S. Kikuchi, S. Kuroda, R. Yoshida, H. Tazawa, T. Fujiwara
    • Organizer
      AACR Annual Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Neutrophil extracellular traps promote liver metastasis of gastrointestinal cancer through the induction of EMT.2019

    • Author(s)
      H. Kajioka, S. Kagawa, A. Ito, K. Kuwada, S. Kikuchi, S. Kuroda, R. Yoshida, H. Tazawa, T. Fujiwara
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Extracellular vesicles in the ascites from gastric cancer patients play critical roles to promote peritoneal dissemination in the intraperitoneal cancer microenvironment2018

    • Author(s)
      Atene Ito, shunsuke kagawa, Shuichi Sakamoto, Kazuya Kuwada, Satoru Kikuchi, Shinji Kuroda, Ryuichi Yoshida, Hiroshi Tazawa and Toshiyoshi Fujiwara
    • Organizer
      AACR Annual Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] IL6 derived from intraperitoneal macrophages is involved in peritoneal dissemination of gastric cancer2018

    • Author(s)
      Shunsuke Kagawa, Shuichi Sakamoto, Kazuya Kuwada, Atene Ito, Hiroki Kajioka, Shinji Kuroda, Satoru Kikuchi, Ryuichi Yoshida, Hiroshi Tazawa, Toshiyoshi Fujiwara
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Extracellular vesicles from gastric cancer promote peritoneal dissemination via M2 differentiation of macrophages.2018

    • Author(s)
      Atene Ito, Shunsuke Kagawa, Hiroki Kajioka, Shuichi Sakamoto, Kazuya Kuwada, Satoru Kikuchi, Shinji Kuroda, Masahiko Nishizaki, Ryuichi Yoshida, Hiroshi Tazawa, Toshiyoshi Fujiwara
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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