Background: 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.
New methods: 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).
Results: 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.
Comparison with existing methods: No orthotopic meningioma models with genetically-engineered cell pairs are available so far.
Conclusion: 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.
Keywords: Crispr/Cas; Meningioma; Neurofibromatosis type 2 (NF2).
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