CNSC-11. T-TYPE CALCIUM CHANNELS DRIVE GLIOBLASTOMA GROWTH BY PROMOTING NEURONAL INTERACTIONS

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor with a dismal median survival of 15 months. Calcium signaling regulates plethora cellular processes making it an ideal target for therapeutic intervention. T-type calcium channels (TTCCs) are low voltage gated expressed in various types neurons throughout regulating glutamatergic synaptic transmission. Our group identified as upregulated GBM cells, stem cells and human tumors. Utilizing FDA repurposed TTCC blocker mibefradil we demonstrated that inhibition TTCCs decreases malignancy parameters. To further elucidate mechanisms action TTCC, treated glioma (GSCs) followed by RNA-sequencing. Analysis transcriptome revealed downregulated genes associated neuronal including synapse organization, postsynaptic density synapses. The effects on led us to examine role promoting growth. Genetic loss Cav3.2 via knockout (KO) microenvironment mice xenografted syngeneic cell lines exhibited delayed progression. KO 5.5-fold reduction volume measured MRI increase compared WT mice. tumors decrease proliferation Ki67+ Cav3.2KO exhibit fewer connections between immunofluorescence. test roles GBM, isolated neuron-GBM co-cultures. co-cultures significant Additionally, projections These data uncover new interactions