梅林(蛋白质)
2型神经纤维瘤病
转染
癌症研究
脑膜瘤
清脆的
生物
细胞培养
神经纤维瘤病
基因
细胞生物学
医学
病理
遗传学
抑制器
作者
Natalie Waldt,Christoph Kesseler,Paula Fala,Peter John,Elmar Kirches,Frank Angenstein,Christian Mawrin
标识
DOI:10.1016/j.jneumeth.2021.109141
摘要
Alterations of the neurofibromatosis type 2 gene (NF2) occur in more than fifty percent of sporadic meningiomas. Meningiomas develop frequently in the setting of the hereditary tumor syndrome NF2. Investigation of potential drug-based treatment options has been limited by the lack of appropriate in vitro and in vivo models. Using Crispr/Cas gene editing, of the malignant meningioma cell line IOMM-Lee, we generated a pair of cell clones characterized by either stable knockout of NF2 and loss of the protein product merlin or retained merlin protein (transfected control without gRNA). IOMM-Lee cells lacking NF2 showed reduced apoptosis and formed bigger colonies compared to control IOMM-Lee cells. Treatment of non-transfected IOMM-Lee cells with the focal adhesion kinase (FAK) inhibitor GSK2256098 resulted in reduced colony sizes. Orthotopic mouse xenografts showed the formation of convexity tumors typical for meningiomas with NF2-depleted and control cells. No orthotopic meningioma models with genetically-engineered cell pairs are available so far. Our model based on Crispr/Cas-based gene editing provides paired meningioma cells suitable to study functional consequences and therapeutic accessibility of NF2/merlin loss.
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