Elucidation of hematogenous metastasis control in gastric cancer related to inflammasome mechanism and development of novel therapeutic agents

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18127
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nagoya City University
• Principal Investigator: Hiroyuki Sagawa 名古屋市立大学, 医薬学総合研究院(医学), 助教 (60645092)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 胃癌 / 転移性肝腫瘍 / 血行性転移 / インフラマソーム / Bex1遺伝子 / 胃肝様腺癌 / AFP産生胃癌

Outline of Final Research Achievements

We demonstrated the involvement of inflammasome in nonalcoholic steatohepatitis (NASH) carcinogenesis and identified brain expressed, X-linked 1 (Bex1) as a NASH carcinogenesis-related gene. In situ hybridization of hepatocellular carcinoma, transfection of Bex1 into a normal rat hepatocyte cell line, and suppression of Bex1 expression in a rat hepatocellular carcinoma cell line showed the involvement of Bex-1 in liver tumor growth. Gastric hepatoid adenocarcinoma and AFP-producing gastric carcinoma were selected from 1,100 gastric cancer cases to elucidate the mechanism of hematogenous metastasis, and liver metastatic gastric carcinoma, gastric hepatoid adenocarcinoma, and AFP-producing tumor were selected.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

胃癌の再発形式には，腹膜播種，リンパ節転移，血行性転移が挙げられ，再発機構によって治療法を選択できる状況が望ましいものの，分子標的薬を含め再発症例という枠組みでの治療法しか現状存在しない．治療法の細分化が必要となる発案契機になった可能性がある．血行性転移のメカニズムを解明する上で，胃肝様腺癌は，胃の組織でありながら肝細胞癌に類似した腫瘍細胞を発生し，早期から高頻度に転移性肝腫瘍をきたす双方の観点から、AFP産生胃癌とともに腫瘍性増殖能ならびに血行性転移メカニズム解明に注目すべき病態である可能性を示した．