Establishment of the H8T-MG Meningioma Cell Line and Integrated Transcriptomics Reveal a Metabolic-Immune Signature in Diploid Transitional WHO Grade 1 Tumours.
Аннотация
Meningiomas are the most common intracranial tumours, yet the molecular programs underlying WHO grade 1 subtypes-particularly transitional diploid tumours-remain insufficiently defined, partly due to the scarcity of biologically faithful in vitro models. Here, we report the establishment of a long-term, genetically unmanipulated grade 1 meningioma cell line (H8T-MG) maintained under normoxic conditions in serum-containing, growth-factor-supplemented medium, together with a complementary long-term primary culture (H16T-MG), and provide an integrated descriptive and functional characterization of these models, combined with a subtype-restricted transcriptomic analysis of diploid transitional grade 1 tumours versus normal meninges. Both cultures preserved the dual meso-neuroectodermal identity characteristic of meningothelial cells, exhibiting stable adherent growth, preserved contact inhibition and a coherent immunocytochemical profile, expressing vimentin, α-SMA, nestin, connexin-43 and cannabinoid receptors-reported here for the first time in grade 1 meningioma cultures-highlighting cannabinoid-related pathways as potential targets for exploration. Transcriptomic analysis identified 51 differentially expressed genes, revealing a coherent inflammatory-metabolic programme characterised by downregulation of IL-17 and TNF signalling, cytokines and chemokines (IL6, CCL2, SELE, S100A8), together with reduced extracellular-matrix and cytoskeletal activity. In parallel, the enrichment of arachidonic acid metabolism, cytochrome-P450/xenobiotic pathways, retinol metabolism and oxidative/epoxygenase activity indicated a lipid/xenobiotic-oriented metabolic shift distinctive of this subtype. Protein-protein interaction analysis identified four hub genes-ASPN, SELE, ACKR1 and ABCB1-integrating ECM remodelling, endothelial-immune modulation and xenobiotic transport, reinforcing an immune-attenuated, metabolically adapted tumour landscape. Collectively, these findings provide the first integrated in vitro and transcriptomic characterisation of diploid transitional meningiomas, underscore the value of biologically stable models for early-stage meningioma research, and support the value of histological and ploidy stratification in grade 1 meningioma biology.
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Обработка статьи · этапы, ошибки и управление
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История · было → стало
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