Impact of intraperitoneal tumor microenvironment on peritoneal dissemination of gastric cancer via involvement of extracellular vesicles

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08679
• 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: Kagawa Shunsuke 岡山大学, 大学病院, 准教授 (00362971)
• Co-Investigator(Kenkyū-buntansha): 吉田 龍一 岡山大学, 大学病院, 助教 (80534768)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 胃癌 / 腹膜播種 / 細胞外小胞体 / 腫瘍微小環境

Outline of Final Research Achievements

Macrophages promoting tumor progression are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination. In this study, we investigated the effect of gastric cancer-derived extracellular vesicles (EVs) on the mechanism by which macrophages differentiate into tumor-promoting forms. EV was extracted from ascites of the gastric cancer patient and culture supernatant of the gastric cancer cell. Their purified EVs induced differentiation into tumor-promoting macrophages when applied to peripheral blood mononuclear cells. Macrophages differentiated with gastric cancer-derived EVs promoted the migration of gastric cancer cells, and these EVs possessed STAT3 protein. These results suggest that gastric carcinoma-derived EVs can affect macrophage differentiation and are factors that form the peritoneal environment to promote tumors.

Free Research Field

消化器癌の新規治療開発

Academic Significance and Societal Importance of the Research Achievements

治療法の進歩にもかかわらず、胃癌の腹膜播種は今なお極めて難治である。新たな治療戦略の開発のために新たな病態の解明が求められている。その病態の新たな側面を解明するため、本研究では腹腔内環境に着目して解析した。我々の研究では胃癌患者の腹腔内に存在している細胞外小胞体が、マクロファージに作用し、腫瘍を促進する腹腔内環境の形成に加担していることを示すことができ、胃癌腹膜播種の病態解明につながる新しい知見が得られた。