2023 Fiscal Year Final Research Report
Treatment Strategies for Glioblastoma with YAP/TAZ-TEAD Inhibitors to Improve the Mesenchymal Microenvironment
| Project/Area Number |
22K16660
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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 (2023)
National Cancer Center Japan (2022) |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | 膠芽腫 / 腫瘍微少環境 / 単一細胞解析 |
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| Outline of Final Research Achievements |
Single-cell RNA sequencing with additional spatial information was performed on human glioblastoma specimens collected by multisampling. Sequence analysis was performed using specimens from 14 locations in 4 glioblastoma cases. We confirmed the heterogeneity of the cellular composition of glioblastoma specimens, with macrophages in the central part of the tumor and oligodendrocyte precursor cells in the deeper part of the tumor. We also confirmed heterogeneity in gene expression patterns of glioblastoma cells such as Mesenchymal-like, Astrocyte-like, Oligodendrocyte precursor cell-like, and Neural precursor cell-like, depending on the collection site.
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| Free Research Field |
脳神経外科
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| Academic Significance and Societal Importance of the Research Achievements |
膠芽腫は治療困難な原発性脳腫瘍である。膠芽腫の腫瘍内では、異なる性質を有する腫瘍細胞クローン がそれぞれ独立して遺伝子変異を獲得しながら増殖・分化し、その中の一部が治療抵抗性・高悪性度化・ 浸潤・播種に関わる機能を獲得し拡大する。その過程で、腫瘍細胞と腫瘍関連マクロファージなどが相互作用することで、間葉系微小環境が形成され、治療抵抗性に関与することも明らかになった。従って、膠芽腫の進化及び腫瘍内不均一性の獲得機構を解明することが、新たな治療戦略を構築するためには有用である。
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