Crispr/Cas-based modeling of NF2 loss in meningioma cells.
J Neurosci Methods
; 356: 109141, 2021 05 15.
Article
em En
| MEDLINE
| ID: mdl-33753124
ABSTRACT
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. NEWMETHODS:
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 EXISTINGMETHODS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Meníngeas
/
Meningioma
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article