Abstract
BackgroundMeningiomas are the second most common primary tumors of the central nervous system. However, there is a paucity of data on meningioma biology due to the lack of suitable preclinical in vitro and in vivo models. In this study, we report the establishment and characterization of patient-derived, spontaneously immortalized cancer cell lines derived from World Health Organization (WHO) grade I and atypical WHO grade II meningiomas.MethodsWe evaluated high-resolution 3T MRI neuroimaging findings in meningioma patients which were followed by histological analysis. RT-qPCR and immunostaining analyses were performed to determine the expression levels of meningioma-related factors. Additionally, flow cytometry and sorting assays were conducted to investigate and isolate the CD133 and CD44 positive cells from primary atypical meningioma cells. Further, we compared the gene expression profiles of meningiomas and cell lines derived from them by performing whole-exome sequencing of the blood and tumor samples from the patients, and the primary cancer cell lines established from the meningioma tumor.ResultsOur results were consistent with earlier studies that reported mutations in NF2, SMO, and AKT1 genes in atypical meningiomas, and we also observed mutations in MYBL2, a gene that was recently discovered. Significantly, the genomic signature was consistent between the atypical meningioma cancer cell lines and the tumor and blood samples from the patient.ConclusionOur results lead us to conclude that established meningioma cell lines with a genomic signature identical to tumors might be a valuable tool for understanding meningioma tumor biology, and for screening therapeutic agents to treat recurrent meningiomas.
Highlights
Meningiomas are the second most common primary tumors of the central nervous system
Cells were cultured in N2/B27 medium, which is composed of Dulbecco’s modified Eagle’s medium (DMEM)/F12 medium supplemented with 1 × B27, 0.5 × N2, 1% non-essential amino acids, 1% glutamine, 0.1 mM β-mercaptoethanol, 1% antibiotic–antimycotic, 10 ng/ml EGF, and 4 ng/ml FGF-2 (Invitrogen Corporation) under 3% O2 and 5% CO2
Characterization of atypical meningioma cancer cell line To analyze the characteristics of grade II meningioma, we focused on the atypical meningiomaderived primary cancer cell line
Summary
Meningiomas are the second most common primary tumors of the central nervous system. There is a paucity of data on meningioma biology due to the lack of suitable preclinical in vitro and in vivo models. We report the establishment and characterization of patient-derived, spontaneously immortalized cancer cell lines derived from World Health Organization (WHO) grade I and atypical WHO grade II meningiomas. The available atypical meningioma cell lines have been artificially-immortalized by viral transduction to induce in vivo expression of the human telomerase reverse transcriptase gene (hTERT), human papillomavirus E6/E7 oncogenes, or SV40 large T antigen. The use of these cell lines as a meningioma model comes with the caveat that it is difficult to know how artificial immortalization might impact the biology of these tumors
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