Dynamic function analysis of cancer-associated carbohydrate complexes on the cell surface and extracellular vesicles in the generation/secretion and their action

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02699
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Chubu University
• Principal Investigator: Furukawa Koichi 中部大学, 生命健康科学部, 特定教授 (80211530)
• Co-Investigator(Kenkyū-buntansha): 大海 雄介 中部大学, 生命健康科学部, 助教 (10584758) ; 古川 圭子 中部大学, 生命健康科学部, 教授 (50260732)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 癌関連糖鎖 / 複合体 / ミクロドメイン / 細胞外小胞 / 脂質ラフト / シグナル

Outline of Final Research Achievements

Cancer-associated glycolipids are not only targets of cancer diagnosis and treatment, but are involved in the regulation of cell signals and phenotypes. As for extracellular vesicles (EVs), they are small vesicles with diameters, 40-150 nm, and exerting cell-cell communications. They also play roles in the regulation of cancer microenvironments and niche formation of cancer metastasis. To clarify the substantial basis of lipid rafts and EVs, proteome study of both fractions was performed, showing highly common molecular profiles. EMARS analyses revealed characteristic clustering molecules around individual glycolipids, i.e., melanoma-specific GD3/GD2 showed high localization of integrins around them. Furthermore, these EVs triggered signal activation and enhancement of malignant properties after addition to the target cells, suggesting that cancer-associated glycolipids affect EV characters, and regulate cancer cell populations.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

癌は人類の健康上の最大の共通課題となっている。通常の外科療法、化学療法、放射線治療に加えて、免疫治療の意義が実証され、期待が大きくなっている。その中で、癌特異的糖鎖抗原の癌診断と治療の標的としての意義に加えて、癌の悪性形質において果たす役割が明らかになりつつある。本研究で明らかになった、酸性糖脂質の細胞膜とEVにおけるシグナルと癌形質制御機能に関する新知見は、単なる癌マーカーの域を超えて、癌の悪性形質を増強する重要因子としての役割が理解されるとともに、癌の根本治療法の開発の上で貴重な視点を提供する点、意義は甚大である。