Analysis of regulation mechanism of CL-18.2 expression in gastric cancer.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07640
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Ito Tatsuya 札幌医科大学, 医学部, 助教 (10516636)
• Co-Investigator(Kenkyū-buntansha): 高澤 啓 札幌医科大学, 医学部, 准教授 (00593021) ; 竹政 伊知朗 札幌医科大学, 医学部, 教授 (50379252) ; 信岡 隆幸 札幌医科大学, 医学部, 講師 (50404603)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 胃癌 / claudin-18.2 / 薬物療法 / 分子生物学的研究

Outline of Final Research Achievements

The aim of this study was to elucidate the expression status and regulatory mechanisms of claudin-18.2 in gastric cancer, targeting the claudin-18.2 protein, which is specifically expressed in gastric mucosa, for antibody therapy. First, we examined the differences in claudin-18.2 expression between primary and metastatic lesions of gastric cancer. As a result, it was found that approximately half of the gastric cancers expressing claudin-18.2 maintained claudin-18.2 expression in metastatic lesions as well. On the other hand, the remaining half showed reduced or lost expression. In gastric cancers expressing claudin-18.2, favorable expression was also observed in the leading edge of the tumor, suggesting a correlation between claudin-18.2 expression and the surrounding microenvironment, as well as the acquisition of metastatic potential.

Free Research Field

細胞分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究期間中に胃癌に対するclaudin-18.2を用いた抗体療法の臨床試験の結果が複数報告され、本邦においても本治療の承認が得られた。一方でclaudin-18.2発現調節機構や、癌における機能については不明である。本研究ではこれらの端緒に触れるも、全貌の解明には至っていない。しかし我々は過去の研究も踏まえ、claudin-18.2蛋白の細胞内局在がこれらを解決する重要な点と考えるとともに、これは実際の治療応用に際しても重要な点になると考ええている。現在、本研究はcell lineを用いた研究に発展・進行中である。