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

2020 Fiscal Year Final Research Report

• 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
• Keywords: 脂肪細胞 / 胃癌

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.

Free Research Field

消化器外科

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。