Development of a glioblastoma treatment based on CLIC2, a protein that inhibits invasion and metastasis of malignant tumors

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16611
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: National Cardiovascular Center Research Institute (2022); Ehime University (2021)
• 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)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: CLIC2 / invasion / metastasis / MMP / brain tumor

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.

Free Research Field

脳腫瘍

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。