| Project/Area Number |
21K16611
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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 | National Cardiovascular Center Research Institute (2022)
Ehime University (2021) |
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Principal Investigator |
Ozaki Saya 国立研究開発法人国立循環器病研究センター, 病院, 専門修練医 (50898799)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | CLIC2 / invasion / metastasis / MMP / brain tumor / 脳腫瘍 / 浸潤 / 血行性転移 / 内皮細胞 / 神経細胞 / マイクログリア |
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| Outline of Research at the Start |
本研究では、Matrix metalloproteinase (MMP)14の抑制を介して悪性腫瘍の浸潤転移に関与すると考えらえるChloride intracellular channel protein 2 (CLIC2)のMMP14活性抑制ドメインを同定し、安全で新規なMMP14阻害剤開発に向けたプロトタイプとなることを示し、膠芽腫の浸潤抑制剤として使用することを目指す。
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| Outline of Final Research Achievements |
CLIC2 was found as a member of a family of chloride ion channel proteins, and its biological significance was unknown. In this study, we show that forced expression of CLIC2 improves prognosis in in vivo experiments using rats. We also showed that CLIC2 localizes to the Golgi apparatus or secretory granules in C6 cells and is secreted extracellularly, and that CLIC2 binds to MMP14 and suppresses its activity, thereby inhibiting metastatic invasion of cancer cells. On the other hand, we found that CLIC2 is mainly expressed in microglia in normal brain tissue and enhances phagocytosis. In addition to suppressing further metastatic invasion of malignant tumors by inducing CLIC2 expression, we are continuing our research to elucidate the function of CLIC2 in microglia in brain tumors.
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| Academic Significance and Societal Importance of the Research Achievements |
がん・悪性腫瘍研究の中でCLIC2の機能を扱った原著論文は少ない。その中で、ラットモデルを用いてCLIC2が悪性腫瘍の転移・浸潤を抑えることを見出し、そのメカニズムがMMP14の活性阻害であることを初めて示した。また、同時に腫瘍細胞内のCLIC2と、正常組織内のCLIC2の働きが異なる可能性についても示した。CLIC2由来ペプチドは、MMP14に限局して作用する画期的な新薬候補となるものと期待している。
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