ESTABLISHMENT OF AN IN VIVO MENINGIOMA MODEL WITH HUMAN TELOMERASE REVERSE TRANSCRIPTASE

Abstract

The lack of meningioma models has hindered research on the pathogenesis and treatment of this commonly diagnosed primary brain tumor. Animal models of meningioma have been difficult to develop, especially those derived from Grade I tumors, which display very slow growth rates, senesce at early passages, and infrequently survive as explants in vivo. In this study, the authors report the establishment of two benign immortalized meningioma cell lines, Me10T and Me3TSC, that can serve as useful models of human meningioma. Tissue specimens obtained at the time of surgery were cultured in vitro and transduced with human telomerase reverse transcriptase/SV40 large T antigen to establish long-term cell lines. The telomeric activity, growth kinetics, immunophenotype, and karyotyping of the cell lines were investigated. The growth inhibitory effects of the antitumor therapies, hydroxyurea and sodium butyrate, on these cell lines were determined. In addition, immortalized cell lines were implanted subdurally into mice to confirm their ability to form tumors. Two immortalized benign meningioma cell lines, Me10T and Me3TSC, transduced with catalytic subunit human telomerase reverse transcriptase alone or human telomerase reverse transcriptase and SV40 large T antigen, were established. The meningeal phenotype of the established cell cultures and orthotopic xenografts was confirmed by immunostaining. After subdural injection into athymic nude mice, both cell lines formed identifiable tumors with histological features and immunostaining patterns of human meningioma. The Me3TSC and Me10T cell lines can serve as useful model systems for biological studies and the evaluation of novel therapies on meningioma.