2020 Fiscal Year Final Research Report
Acidic microenvironment promotes lymphatic metastasis via the functional changes of lymphatic endothelial cells
| Project/Area Number |
18K08580
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 癌微小環境 / 酸性環境 / リンパ節転移 |
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| 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.
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| Free Research Field |
実験病理学
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| 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。
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