2021 Fiscal Year Final Research Report

Mechanisms of metastasis promoted by cancer associated fibroblast via Wnt signal pathway in colorectal cancer

Research Project

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Project/Area Number	19K09188
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Tohoku University
Principal Investigator	MUSHA Hiroaki 東北大学, 医学系研究科, 大学院非常勤講師 (30724322)
Co-Investigator(Kenkyū-buntansha)	唐澤秀明東北大学, 大学病院, 助教 (30547401) 山村明寛東北大学, 大学病院, 助教 (30814678) 内藤剛東北大学, 医学系研究科, 准教授 (50291258) 大沼忍東北大学, 大学病院, 助教 (70451565)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	癌関連線維芽細胞 / Wnt2 / Wnt5a / 大腸癌
Outline of Final Research Achievements	Cancer-associated fibroblasts (CAFs) were obtained from paired CAFs and normal fibroblasts in colorectal cancer (CRC) tissue. Gene expression analysis of CAFs revealed that Wnt2 and Wnt5a were highly expressed in colorectal CAFs. We performed immunohistochemical analysis on Wnt2 and Wnt5a in CRC patients who underwent surgery. High expression of Wnt2 and Wnt5a were significantly associated with the factors which related to cancer progression or metastasis. Subsequent in vitro analyses revealed that cancer cell invasion and migration were significantly decreased in the conditioned medium corrected from immortalized CAFs transfected with siRNA targeting Wnt2. Besides, cancer cell proliferation and migration were significantly increased by stimulation with human recombinant Wnt5a protein. Our findings suggest that Wnt2 and Wnt5a derived CAFs enhances CRC cell invasion and migration and play a crucial role in CRC progression and have potential as a target of anti-cancer therapies.
Free Research Field	消化器外科学
Academic Significance and Societal Importance of the Research Achievements	大腸癌の進行及び転移において癌関連線維芽細胞といわれる癌組織周囲に存在する線維芽細胞が重要な役割を行うことが報告されている。今回の研究ではこの癌関連線維芽細胞における遺伝子発現を解析することにより、Wnt2およびWnt5aが高発現していることを見出した。この遺伝子で大腸癌細胞株を刺激すると、癌の浸潤、転移が促進される可能性が示された。がん細胞そのものだけでなく、この癌関連線維芽細胞が癌の周囲でWnt2やWnt5aを介してがん細胞に働きかけて、癌の進行を促進している可能性を示している。これらの癌周囲の微小環境も新たな治療のターゲットとなる可能性が示唆された。