Roles of exosomes in neuronal circuit reconstruction

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22578
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 51:Brain sciences and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Hanayama Rikinari 金沢大学, ナノ生命科学研究所, 教授 (40403191)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: エクソソーム / 神経膠腫 / ミクログリア / 血管新生

Outline of Final Research Achievements

We have revealed that glioma-derived exosomes convey a tumor-related factor WT1 to microglial cells in the surrounding areas of a tumor leading to angiogenesis (generation of new blood vessels), which contributes to the creation of a microenvironment favorable for invasion and metastasis of a tumor.

Using an intracranial implantation glioma mouse model, we first showed a longer survival time of mice through tumor size reduction and suppression of invasion and metastasis by repressing the production of exosomes by the glioma. Next, we showed that exosomes secreted from the glioma were taken up by the surrounding microglia thus regulating gene expression in microglia, thereby promoting angiogenesis. Furthermore, we showed that WT1, an expression regulator of that gene, was contained in tumor-derived exosomes of human patients and regulated the microglial ability of angiogenesis.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

神経膠腫は脳腫瘍の中で最も悪性度が高く，集学的治療を施しても平均生存期間が約2年と非常に予後が悪い腫瘍である。本研究により、神経膠腫の進展における神経回路の再構築に、エクソソームが深く関与しており、その産生を抑えることで、腫瘍の浸潤・転移を抑えることができる可能性が示された。今後、神経膠腫の早期発見や予後診断、新たな治療法の開発へと研究が発展することが期待される。