Functional Analysis of Meflin in Cancer Fibrosis and Research for Development of Novel Therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03467
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Fujita Health University
• Principal Investigator: Takahashi Masahide 藤田医科大学, その他部局等, 教授 (40183446)
• Co-Investigator(Kenkyū-buntansha): 榎本 篤 名古屋大学, 医学系研究科, 教授 (20432255) ; 浅井 直也 藤田医科大学, 医学部, 教授 (80273233)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん関連線維芽細胞 / Meflin / 膵がん / 大腸がん / 非小細胞肺がん / 泌尿器がん / AM80 / 免疫チェックポイント阻害剤

Outline of Final Research Achievements

In this study, we analyzed the relationship between Meflin expression in cancer-associated fibroblasts (CAFs) in the stroma of pancreatic, colorectal, non-small cell lung, and urologic cancers and cancer prognosis and treatment response. The results showed that the prognosis was significantly higher in the group with higher Meflin positivity in all carcinomas, and that the response rate to chemotherapy was higher in pancreatic cancer, and to IC inhibitors in non-small cell lung cancer and urologic cancer. In addition, Am80, a synthetic non-natural retinoid, was found to be a reagent that can effectively induce Meflin expression in CAFs, indicating that the combination of Am80 and chemotherapy or IC inhibitors can lead to the development of new cancer therapies.

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Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、がん線維化に関わる線維芽細胞の分化と機能におけるMeflinの関与について研究を進め、どのような機序でがんの悪性化を制御しているかを解析した。膵がん、大腸がん、肺がん、泌尿器がんにおける腫瘍内線維芽細胞におけるMeflinの発現と予後との関連、免疫関連細胞の浸潤、化学療法および免疫チェックポイント(IC)阻害剤の効果との関連の解析を行い、Meflin高発現群では患者の予後が有意に良く、治療効果も高いことが判明した。さらに、線維芽細胞におけるMeflinの発現を増強する低分子化合物Am80を同定し、化学療法あるいはIC阻害剤との併用による新たながん治療法開発に資する結果を得た。