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Elucidation of stepwise formation of metastatic niche originating from lymph node marginal sinus of gastric cancer and cancer stromal cell interaction

Research Project

Project/Area Number 16K19088
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionTeikyo University

Principal Investigator

Kikuchi Yoshinao  帝京大学, 医学部, 講師 (90512260)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords癌微小環境 / 癌間質相互作用 / 癌関連線維芽細胞 / 中皮間葉転換 / ペリオスチン / microRNA-21 / 転移前リンパ節 / リンパ管新生 / periostin / miR-21 / エクソソーム / 中皮-間葉転換 / 病理学 / 癌
Outline of Final Research Achievements

There are three pathways of cancer metastasis: hematogenous, lymphatic, and dissemination. In this study, we focused on the environment (cancer microenvironment) surrounding cancer cells in the early stage of lymphatic metastasis. The expression levels of periostin, a secreted protein, and miR-21, a microRNA, released from the gastric cancer microenvironment, are related to the presence of lymph node metastasis. Analysis of these function showed that they play an important role in progression from early lymph node metastasis. In addition, we focused on the similarity between the early stage of lymph node metastasis and the dissemination pathway that spreads in the body cavity. It was clarified that periostin and miR-21 act as a cancer promoter by acting on lymphatic endothelial cells and mesothelial cells that compose the cancer microenvironment.

Academic Significance and Societal Importance of the Research Achievements

本研究は、これまで十分に研究が進んでいなかったリンパ節転移初期段階における癌細胞を取り巻く環境で、ペリオスチンとmiR-21という因子が重要な役割を担っていることを示した。また、これまでリンパ節転移の初期段階と播種の類似性に着目する研究はあまり知られていないが、一見異なった転移経路においても、これらの因子が癌細胞の環境を構成するリンパ管内皮細胞や中皮細胞に同様に作用する事が示された。本研究の成果により、ペリオスチンやmiR-21が転移を予測するマーカーとして応用されることが期待されるだけでなく、転移治療の標的因子となる可能性も示唆された。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results)

  • [Journal Article] Clinicopathological significance of microRNA-21 in extracellular vesicles of pleural lavage fluid of lung adenocarcinoma and its functions inducing the mesothelial to mesenchymal transition2020

    • Author(s)
      Watabe Shiori、Kikuchi Yoshinao、Morita Shigeki、Komura Daisuke、Numakura Satoe、Kumagai‐Togashi Arisa、Watanabe Masato、Matsutani Noriyuki、Kawamura Masafumi、Yasuda Masanori、Uozaki Hiroshi
    • Journal Title

      Cancer Medicine

      Volume: 9 Issue: 8 Pages: 2879

    • DOI

      10.1002/cam4.2928

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 肺癌における胸腔洗浄液中の細胞外分泌小胞内miR-21の臨床病理学的意義と機能(Clinicopathologic significance and function of extracellular vesicle-miR-21 in pleural lavage of lung cancer)2019

    • Author(s)
      渡部 朱織, 菊地 良直, 森田 茂樹, 河村 大輔, 沼倉 里枝, 渡邉 雅人, 松谷 哲行, 川村 雅文, 安田 政実, 宇於崎 宏
    • Organizer
      日本癌学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肺癌胸腔洗浄液中のエクソソーム内miR-21発現量は細胞診判定と胸膜浸潤を判定する2018

    • Author(s)
      渡部朱織, 菊地良直, 森田茂樹, 富樫有紗, 渡邊雅人, 松谷哲行, 河村雅文, 安田政実, 宇於崎宏
    • Organizer
      日本臨床細胞学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 胃癌間質におけるCD90発現の意義2018

    • Author(s)
      沼倉里枝, 西東瑠璃, 富樫有紗, 渡部朱織, 渡邊雅人, 菊地良直, 宇於崎宏
    • Organizer
      日本病理学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺腺癌組織および術前胸腔洗浄液中細胞外分泌小胞に含まれるmiR-21の発現は胸膜浸潤と相関する2018

    • Author(s)
      渡部朱織, 菊地良直, 富樫有紗, 渡邉雅人, 松谷哲行, 河村雅文, 安田政実, 宇於崎宏
    • Organizer
      日本病理学会
    • Related Report
      2018 Research-status Report 2017 Research-status Report
  • [Presentation] 尿路上皮癌間質におけるCD10、Periostin、Podoplaninの発現2017

    • Author(s)
      熊谷有紗, 渡部朱織, 渡邉雅人, 菊地良直, 宇於崎宏
    • Organizer
      日本病理学会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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