Analysis of Cancer Stem Cell Induction Ability in the Microenvironment of Glioblastoma Focused on NFATc4

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09152
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Yamaguchi University
• Principal Investigator: Cui Dan 山口大学, 大学院医学系研究科, 准教授 (40346549)
• Co-Investigator(Kenkyū-buntansha): 池田 栄二 山口大学, 大学院医学系研究科, 教授 (30232177) ; 吉冨 千尋 山口大学, 大学院医学系研究科, 助教 (50819323) ; 田中 瑛 山口大学, 大学院医学系研究科, 助教 (60913936)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膠芽腫 / 腫瘍幹細胞 / 低酸素 / 低栄養

Outline of Final Research Achievements

Glioblastoma is one of the most malignant primary brain tumors with a poor prognosis and is refractory to treatment. Accumulative evidence indicates that tumor stem cells are a cause of the treatment resistance and recurrence of glioblastoma. The induction mechanism of tumor cells has not yet been fully understood. Here, we have produced a spheroid that reproduces the microenvironment of human glioblastoma tissue using the human glioblastoma cell line U87. Necroses was observed in the central part of the spheroid cultured under hypoxic, and a high frequency of NFATc4 expression was also seen in the nuclei of cancer stem cells surrounding the necroses. Furthermore, we transplanted spheroids with high expression of NFATc4 into the brains of nude mice.

Free Research Field

実験病理

Academic Significance and Societal Importance of the Research Achievements

膠芽腫は悪性度が高く、放射線療法および化学療法に抵抗性を示す極めて予後不良な悪性腫瘍である。本研究計画では、壊死周囲ニッチにおけるNFATc4の果たす役割を中心に解析し、治療標的分子としてのNFATc4の有用性を明らかにすることで、患者の予後改善さらには腫瘍の根治の向けた新規治療法開発につながる。