Molecular mechanism of peritoneal metastasis via adipocytes in gastric cancer Peritoneal metastasis via adipocytes in gastric cancer

Research Project

Project/Area Number	18K16324
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	University of Yamanashi (2019-2020) Kyoto Prefectural University of Medicine (2018)
Principal Investigator	SHODA Katsutoshi 山梨大学, 大学院総合研究部, 助教 (70783421)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	脂肪細胞 / 胃癌 / exosome / 腹膜播種 / 大網 / バイオマーカー
Outline of Final Research Achievements	Extracellular vesicles (EV) could become the trigger for peritoneal metastasis. In the present study, we aim to elucidate the molecular mechanism of EV-mediated intercellular communication between adipocytes abundantly present in the peritoneal cavity and gastric cancer cells and peritoneal mesothelial cells. Comprehensive analysis of changes in the expression of adipocytes co-cultured with gastric cancer cells revealed increased expression of molecules involved in inflammation, including CXCL1 and IL6. In addition, it was confirmed that CXCL1 and IL6 are contained in large amounts in EV extracted from adipocyte medium co-cultured with gastric cancer cells. Furthermore, CXCL1 expression in omentum was found to be significantly correlated with tumor depth (p = 0.001) and peritoneal metastasis (p = 0.009). We demonstrated the possibility that adipocytes could be involved in acquiring the metastatic potential of cancer cells by intercellular communication with gastric cancer cells.
Academic Significance and Societal Importance of the Research Achievements	腹腔内に豊富に存在する脂肪細胞と胃癌細胞や腹膜中皮細胞との、EVを介した細胞間情報伝達に着眼し、その分子機序解明により脂肪細胞を標的とした新規治療の可能性を示した。腹膜播種形成予測に有用な新規バイオマーカーとなりうるばかりでなく、難治性胃癌の個別化医療推進に資する脂肪細胞を標的とした新規治療法の開発につながることが期待される。