Maintenance of tumor microenvironments by extracellular vesicles derived from glioblastoma cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02910
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kanazawa University
• Principal Investigator: Nakada Mitsutoshi 金沢大学, 医学系, 教授 (20334774)
• Co-Investigator(Kenkyū-buntansha): 華山 力成 金沢大学, ナノ生命科学研究所, 教授 (40403191)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 悪性神経膠腫 / 膠芽腫 / エクソソーム / マイクログリア / 細胞外微小環境

Outline of Final Research Achievements

Glioblastoma is the most malignant brain tumor. In order to develop new treatments for glioblastoma, it is necessary to elucidate the mechanism of tumor growth and progression. Recently, extracellular vesicles called exosomes, which are secreted by cells, have been attracting attention in various malignant tumors. In this study, we studied the exosomes secreted by glioblastoma cells. We found that the exosomes containing WT1 protein are secreted by glioblastoma cells, then expression of thrombospondin-1, a negative regulator of angiogenesis, was downregulated in surrounding microglia. This intercellular regulatory pathway promotes glioblastoma progression. Our findings establish a novel model of tumor progression via exosome-mediated WT1-Thbs1, which may be a future diagnostic or therapeutic target.

Free Research Field

脳腫瘍学

Academic Significance and Societal Importance of the Research Achievements

今回の研究により、これまでは知られていなかった膠芽腫とエクソソームの関係が明らとなり、さらにそのメカニズムを細胞レベルだけではなく、生体レベルでも解明することができた。膠芽腫細胞のエクソソーム分泌を抑制するあるいは、そのエクソソームの中に含まれるタンパク質の量を変化させることで、膠芽腫細胞が形成する腫瘍の大きさを縮小し、その生命予後を改善させることが動物実験で証明できた。この研究結果を応用することで、従来の膠芽腫に対する治療とは一線を画する革新的な膠芽腫治療法を提案できる可能性がある。