Functional analysis of Crk and Exosome in determining the metastatic organ of cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07059
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Hokkaido University
• Principal Investigator: Tsuda Masumi 北海道大学, 医学研究院, 准教授 (30431307)
• Co-Investigator(Kenkyū-buntansha): 田中 伸哉 北海道大学, 医学研究院, 教授 (70261287) ; 王 磊 北海道大学, 医学研究院, 助教 (70637975)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: がん / 転移 / エクソソーム / Crk / ErbB2 / アダプター分子

Outline of Final Research Achievements

According to this study, it has shown that the adapter molecule Crk controls the kinds and amount of inclusion molecules in exosomes. The exosomes derived from Crk-expressing bladder cancer cells contain ErbB2 together with Crk, and acts on the vascular endothelial cell of the lung of the metastatic organ, which contributes to the development of the lung metastasis of bladder cancer cells. This suggests that Crk and ErbB2 contained in exosomes activate the signal transduction pathway of recipient cells of the metastatic organ and change their characteristics. Many cancers with high expression of Crk have been reported, which suggests that heterogenity is also created for exosome inclusion molecules, which may contribute to the selection and establishment of cancer metastasis.

Free Research Field

がんの転移

Academic Significance and Societal Importance of the Research Achievements

本研究により、アダプター分子Crkはがん細胞の悪性形質のみならず、エクソソームを介してがんの転移先臓器の再構築と転移形成にも関与することが明らかとなった。これは、アダプター分子がエクソソームを介して転移先臓器の組織環境を整備し、がん転移の成立と促進に寄与することを示す画期的なデータである。現在、Crkとシグナル下流分子C3Gの結合を阻害する薬剤を開発検討中であり、エクソソームにおける効果を検証後は、がん細胞の増殖のみならずエクソソームを介したがんの浸潤・転移を抑制できる可能性があり、多くのがん患者の生命予後の改善に貢献できることが期待される。