Regulatory mechanisms for microenvironment and metastasis of cancers with glycosphigolipids via extracellular vesicles

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19616
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: Chubu University
• Principal Investigator: FURUKAWA Koichi 中部大学, 生命健康科学部, 教授 (80211530)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: エクソソーム / 糖脂質 / ガングリオシド / インテグリン / GD3

Outline of Final Research Achievements

Using cancer-associated glycolipid-expressing cell lines and their normal counterparts (control), secreted amounts of exosomes and levels of contained glycolipids and associated membrane proteins were analyzed. Consequently, in multiple cell line systems, exosomes derived from GD3-expressing cell lines expressed much higher amounts of integrin isoforms than those from individual GD3-negative controls. There were no definite differences in the integrin expression levels in the cell lysates between GD3-positive and GD3-negative cell lines. In the analysis of EGF receptor levels as measured similarly, they showed increase in GD3-expressing cell lines in both cell lysates and secreted exosomes. Now, we are analyzing composition of glycosphingolipids in exosomes, and also their functions.

Free Research Field

生化学、糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

癌関連糖脂質が、腫瘍マーカーとしてのみならず、癌細胞の悪性形質に重要な役割を果たすことが示されてきたが、本研究では、癌関連糖脂質を発現する細胞由来の細胞外分泌顆粒であるエクソソームが、接着受容体であるインテグリンを著明に多く含んでいることが判明した。このことから、癌細胞の浸潤、転移等の悪性形質において、細胞膜表面のみならず、癌関連糖脂質とインテグリンがエクソソームにおいても会合して、悪性形質に重要な役割を果たしていることが示唆された。とくに転移の予防においてエクソソームが標的になりうることを示唆する結果である。