2021 Fiscal Year Final Research Report
Tumor microenvironment remodeling by YAP/TAZ in glioblastoma
| Project/Area Number |
20K17969
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | 分化型膠芽腫細胞 / CCN1 / 微小環境 / マクロファージ / YAP/TAZ / TEAD / 膠芽腫幹細胞 / 間葉系サブタイプ |
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| Outline of Final Research Achievements |
Glioblastoma (GBM) is the most aggressive brain tumor and is composed of a variety of tumor cells, including GBM stem cells (GSCs) and differentiated GBM cells (DGCs). In this study, we investigated the role of DGCs in the microenvironment by comparing gene expression data of GSCs and DGCs to identify a group of genes that are characteristic of DGCs. Co-transplantation of DGCs and GSCs resulted in decreased survival and increased macrophage infiltration in tumor tissue in a mouse brain tumor model compared to GSCs alone. DGC promoted macrophage infiltration via the YAP/TAZ-TEAD-CCN1 pathway, contributing to GBM progression.
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| Free Research Field |
脳神経外科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、GSCが分化することにより生成されるDGCがマクロファージを中心とした間葉系微小環境構築における重要な因子であることを明らかにした。本研究によりDGCがGSCと協調してGBMの進展に寄与するということ示され、GSCだけでなくDGCを含めた腫瘍内不均一性に対応した治療戦略の重要性が明らかになった。YAP/TAZ-TEADの抑制により、DGCによる微小環境改変が阻止され、GBMの新たな治療戦略に繋がる可能性が本研究によって示唆された
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