Negative spiral mechanism of cancer associated microenvironment i

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09173
• 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: Okayama University
• Principal Investigator: Shirakawa Yasuhiro 岡山大学, 医学部, 客員研究員 (60379774)
• Co-Investigator(Kenkyū-buntansha): 野間 和広 岡山大学, 大学病院, 講師 (10534761)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 癌微小環境 / 癌関連線維芽細胞 / 化学療法 / 放射線療法

Outline of Final Research Achievements

Chemotherapy and radiotherapy were applied to esophageal fibroblasts in vitro to verify the presence or absence of differentiation into myofibroblast. The expression of αSMA and FAP was increased, suggesting that antitumor treatment induces differentiation into myofibroblast. Irradiated fibroblasts tended to increase the proliferative capacity and radiosensitivity of cancer cell lines. Invasion assay and migration assay increased infiltration and migration ability, especially in squamous cell carcinoma cell lines. The supernatants of treatment-induced CAFs were subjected to a cytokine array and compared with normal fibroblasts. In particular, IL6 increased in various cell lines, and reproducibility could be confirmed.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、標準的治療が副次的にCAFsの作用増強に繋がっている可能性が示された。現在の標準的治療の治療前に我々の開発してきたPIT治療などCAFsを標的とした治療を施すことで、さらに治療効果を上乗せする革新的な癌治療の開発に繋がると予想される。既に食道癌に限らず膵癌や大腸癌など他の固形癌においてもCAFsの同様な知見が多数得られており、今後多くの癌腫に対応できる大きな可能性を秘めており極めて研究意義の高いものと考えている。