Are glycans expressed on exosome involved in target organ specificity in cancer metastasis?

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16682
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Hirosaki University
• Principal Investigator: Ayumu Kusaka 弘前大学, 医学研究科, 客員研究員 (40815776)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: エキソソーム / 糖鎖解析

Outline of Final Research Achievements

The development of effective molecular biomarkers is urgently needed, since urothelial carcinoma has a high recurrence rate and a remarkably poor prognosis after recurrence. Recently, it has been suggested that cancer cells secrete exosomes prior to metastasis to create a viable environment (pre-metastatic niche) in order to establish metastasis. This observation suggested that the organ selectivity of cancer may be determined by exosomes, and if exosomes can be detected in the course of treatment, it may be possible to predict which organs are likely to metastasize. We investigated the expression of exosomal glycans and integrins in mouse experiments and clinical specimens using exosomes from bladder cancer cell lines. The results suggest that exosomal glycans may differ in clinical specimens in a disease-specific manner.

Free Research Field

泌尿器癌

Academic Significance and Societal Importance of the Research Achievements

本研究では尿路上皮癌細胞株のエキソソームを蛍光標識し、マウスに投与することにより、エキソソームの分布についての初期検討を行った。続いて患者検体を用いて、臨床検体における臓器特異的なエキソソームの検出と検証を行った。その結果、エキソソーム糖鎖は、疾患毎に違いあることが示唆された。エキソソーム糖鎖を検討した報告は本研究が初であり、学術的意義や社会的意義は大きい。これら変化の意義は更なる追加研究を必要とするが、我々が同定したエキソソーム糖鎖についての検討は、癌の転移機序についての新しい知見に関与する可能性があり、今後の発展に期待が持てる結果である。