Identification of molecular mechanism underlying inflammatory-related carcinogenesis through activating the stroma in gastric cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08543
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Miyake Keisuke 熊本大学, 病院, リサーチ・スペシャリスト (10814759)
• Co-Investigator(Kenkyū-buntansha): 石本 崇胤 熊本大学, 病院, 特任准教授 (00594889) ; 有馬 浩太 熊本大学, 病院, 非常勤診療医師 (10792616) ; 泉 大輔 熊本大学, 病院, 非常勤診療医師 (60594877) ; 今村 裕 公益財団法人がん研究会, 有明病院 消化器外科, 医長 (70583045) ; 日比 泰造 熊本大学, 大学院生命科学研究部(医), 教授 (10338072)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 胃癌 / 癌関連線維芽細胞 / 腫瘍間質

Outline of Final Research Achievements

The purpose of this study was to clarify the molecular mechanism of gastric cancer carcinogenesis and progression caused as a result of stromal cell reactivity and stromal activation in an inflammatory environment. First, fibroblasts were stimulated with inflammatory cytokines, and the culture supernatant was used to stimulate gastric cancer cells. As a result, the cytokine-stimulated culture supernatant was more proliferative and infiltrative than the unstimulated culture supernatant. It turned out to promote. Subsequent comprehensive gene expression analysis by RNA-Seq revealed that activated fibroblasts promote the growth of gastric cancer through the secretion of IL-6, IL-24 and LIF. From the above results, it was clarified that chronic inflammation activates fibroblasts and enhances the growth and infiltration of gastric cancer through secretions at present.

Free Research Field

腫瘍生物学、消化器外科学

Academic Significance and Societal Importance of the Research Achievements

これまで腫瘍微小環境に存在する線維芽細胞（CAFs）の働きによって癌細胞の増殖・浸潤が増長されることが報告されてきたが、本研究によって慢性炎症による繊維芽細胞の活性化が癌細胞のさらなる増殖・浸潤の増長を引き起こすことを明らかにした。