Elucidation of the mechanism of the physiological functions via Tensin1 in lung cancer-associated fibroblasts

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16310
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Juntendo University
• Principal Investigator: Honma Yuichiro 順天堂大学, 医学部, 非常勤助教 (70869247)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: がん関連線維芽細胞 / 肺がん / tensin1 / tensin3

Outline of Final Research Achievements

Cancer-associated fibroblasts (CAF) play a crucial role in cancer progression. Here, we identified and focused on the role of tensin family member, TNS1 (tensin1) and TNS3 (tensin3), mediated CAF bioactivities as the new CAF specific marker. CAFs increase the expression of tensin1 and 3 and increased tensin1 expression in cancer stroma was associated with tumor recurrence resected from non-small cell lung cancer patients. Furthermore, increased expression of c-Met and its ligand hepatocyte growth factor (HGF) release in CAFs suggested over-expressed tensin3 CAFs may lead to the cancer development. Transforming growth factor (TGF)-β1 profoundly up-regulates tensin1 expression in fibroblasts through Src signaling and dasatinb, Src inhibitor disrupted TGF-induced CAFs-mediated contraction of collagen gels and migration by suppressed tensin1. Dasatinib may be a promising as a novel anti-cancer stroma strategy, by targetting the TNS1+/TNS3+ CAF.

Free Research Field

肺がん

Academic Significance and Societal Importance of the Research Achievements

本研究では、CAFの生理機能活性制御因子としてtensin1/3に着目し、新たな視点から癌と癌間質における各種相互作用からも検討した。tensin1/3を介するCAFを標的とした創薬へと繋げることで、従来とは全く異なった新たな治療戦略に発展する可能性が高い。ダサチニブがtensin1/3を介したCAFの生理活性機能を抑制するという、既存の直接癌細胞を標的とする治療法とは全く異なり”癌間質のtensin1/3陽性CAFを標的とした新たな治療戦略”の可能性を提唱した。