Analysis of the function of cancer-associated fibroblasts (CAFs) in the invasion of oral cancer.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10329
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Niigata University
• Principal Investigator: Funayama Akinori 新潟大学, 医歯学総合病院, 講師 (80529686)
• Co-Investigator(Kenkyū-buntansha): 田沼 順一 新潟大学, 医歯学系, 教授 (20305139) ; 泉 健次 新潟大学, 医歯学系, 教授 (80242436) ; 三上 俊彦 新潟大学, 医歯学系, 非常勤研究員 (90595745)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 癌関連線維芽細胞 / 口腔癌 / 癌微小環境 / TGF-β / SOX9

Outline of Final Research Achievements

Cancer-associated fibroblasts (CAFs) have important roles in promoting cancer development and progression. This study developed three-dimensional (3D) in vitro models co-cultured with oral squamous cell carcinoma (OSCC) cells and CAFs to examine CAF-mediated cancer migration and invasion． Moreover, we performed an immunohistochemical analysis of alpha-smooth muscle actin and SOX9 expression in surgical specimens from 65 OSCC patients. The results indicated that CAFs promote cancer migration and invasion in migration assays and 3D in vitro models. The invading OSCC cells exhibited significant SOX9 expression. TGF-β1 signaling inhibition reduced SOX9 expression and cancer invasion. In surgical specimens, the presence of CAFs was correlated with SOX9 expression in the invasive cancer nests and had a significant impact on regional recurrence. These findings demonstrate that CAFs promote cancer migration and invasion via the TGF-β/SOX9 axis.

Free Research Field

口腔外科

Academic Significance and Societal Importance of the Research Achievements

がんの悪性化を制御する CAFs とその細胞が分泌する TGF-βを標的とすることで、がん組織周囲の微小環境も新たにがん治療のターゲットとして加えることができることになり、がん細胞を標的とした抗がん剤との併用による新規治療法開発への応用に期待できる。またCAFsの機能解析がさらに加速して進めていくことで治療方針や予後予測にCAFsの存在を考慮するなどの新たな治療戦略の立案の一助になる可能性がある。