Lectin-containing extracellular vesicles to prevent microenvironment establishment and peritoneal dissemination of scirrhous gastric carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08722
• 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: The Noguchi Institute
• Principal Investigator: Tsuchida Akiko 公益財団法人野口研究所, 研究部, 研究員 (70378024)
• Co-Investigator(Kenkyū-buntansha): 八須 和子 (広瀬和子) 公益財団法人野口研究所, 研究部, 研究員 (30625447) ; 井手尾 浩子 公益財団法人野口研究所, 研究部, 研究員 (90180322)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胃癌 / 腹膜転移 / 細胞外小胞 / 腹膜中皮細胞 / 糖脂質 / 糖転移酵素

Outline of Final Research Achievements

The study initially aimed to elucidate the mechanisms that promote peritoneal metastasis by analysing the function of extracellular vesicles secreted by highly metastatic gastric cancer cells, but no useful information was obtained from the characterisation of the extracellular vesicles. As a next step, we aimed to elucidate the mechanisms that promote intracellular peritoneal dissemination. We investigated glycolipids on the plasma membrane as galectin-4-binding molecules in detail and found that the expression pattern of neutral glycolipids changed significantly in cell lines with different peritoneal seeding potential. Since this characteristic change is regulated by the expression of the glycosyltransferase B3GALT5, we established a stable expression line of B3GALT5 and conducted in vivo experiments. We found that B3GALT5 stable expressed-clones strongly suppressed intraperitoneal tumour formation.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

腹膜転移は、転移性または再発胃癌にしばしば伴い、有効な治療法がないために患者の予後を悪化させる難治性の病態である。従って、腹膜転移を引き起こすメカニズムや分子についての理解を深めることが急務である。
本研究の結果から、B3GALT5安定発現する細胞株では腹腔内の腫瘍形成が強く抑制されたことから、腹腔内に散らばった癌細胞に対して本酵素遺伝子を送達させることできれば、腹膜転移の治療に結び付く可能性が高い。高転移性胃癌の腹膜転移を阻止し、将来的に腹膜転移先の癌を治療できる新規治療薬を創製することで低分化癌の予後を大きく改善でき、治療困難な患者を少しでも減らすことが可能になるであろう。