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Acidic microenvironment promotes lymphatic metastasis via the functional changes of lymphatic endothelial cells

Research Project

Project/Area Number 18K08580
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionWakayama Medical University

Principal Investigator

Nakanishi Masako  和歌山県立医科大学, 医学部, 講師 (60437382)

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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords癌微小環境 / 酸性環境 / リンパ節転移 / VCAM-1 / 酸性微小環境 / リンパ管内皮細胞 / 酸感受性受容体 / アシドーシス / 転移
Outline of Final Research Achievements

Human lymphatic endothelial cells (HDLEC) expressed several acid receptors. Acidic treatment significantly induced the expression of VCAM-1, and this effect was reduced by knockdown of acid-sensing receptor GPR4. In addition, adherence of cancer cells expressing VLA-4 to HDLEC was accelerated by acidic treatment, and the treatment of anti-VCAM-1 antibody inhibited this effect. These results suggest that acidic microenvironment induce VCAM-1 expression via GPR4 on lymphatic endothelial cells and enhance adhesion of cancer cells to promote lymph node metastasis.

Academic Significance and Societal Importance of the Research Achievements

癌の病期の進展ならびに予後を評価する上で、リンパ節転移は重要な因子の一つとなる。従来、リンパ節転移は、癌細胞自身が産生するリンパ管新生因子の発現に左右されると考えられてきた。本研究において明らかとなった、癌組織の酸性環境と、リンパ管内皮細胞におけるGPR4ならびにVCAM-1発現との関連性は、癌の病態形成を考えるうえで新たな知見である。また今後、リンパ節転移の予防・治療標的として、これらの分子の有用性が期待される。

Report

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

    (7 results)

All 2021 2020 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (5 results)

  • [Journal Article] Acidic microenvironment induction of interleukin-8 expression and matrix metalloproteinase-2/-9 activation via acid-sensing ion channel 1 promotes breast cancer cell progression2021

    • Author(s)
      Nakanishi M, Korechika A, Yamakawa H, Kawabe N, Nakai K, Muragaki Y.
    • Journal Title

      Oncol Rep.

      Volume: 45 Issue: 3 Pages: 1284-1294

    • DOI

      10.3892/or.2020.7907

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Gain-of-Function Mutation p53R248W Suppresses Cell Proliferation and Invasion of Oral Squamous Cell Carcinoma through the Down-Regulation of Keratin 172021

    • Author(s)
      Enaka M, Nakanishi M, Muragaki Y.
    • Journal Title

      American Journal of Pathology

      Volume: 191 Issue: 3 Pages: 555-566

    • DOI

      10.1016/j.ajpath.2020.11.011

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 癌組織の酸性微小環境はリンパ管内皮細胞におけるVCAM-1の発現誘導を介してリンパ節転移を促進する2020

    • Author(s)
      中西雅子、池森恭花、村垣泰光
    • Organizer
      第109回日本病理学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Acidic microenvironment promotes lymphatic metastasis via the induction of VCAM-1 in lymphatic endothelial cells.2020

    • Author(s)
      Nakanishi M, Muragaki Y
    • Organizer
      第79回日本癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 癌組織の酸性環境はリンパ管内皮細胞におけるVCAM-1の発現誘導を介してリンパ節転移モデルを転移を促進する2020

    • Author(s)
      中西雅子、池森恭花、村垣泰光
    • Organizer
      第109回日本病理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 乳癌骨転移におけるCPEB3の役割2018

    • Author(s)
      中西雅子、新井理紗、服部綾乃、林真里、波多賢二、米田俊之、村垣泰光
    • Organizer
      第107回日本病理学会
    • Related Report
      2018 Research-status Report
  • [Presentation] The role of CPEB3 in the development of breast cancer bone metastases2018

    • Author(s)
      Masako Nakanishi, Kenji Hata, Yasuteru Muragaki
    • Organizer
      第77回日本癌学会
    • Related Report
      2018 Research-status Report

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

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