Cnsc-18. differential effects of neurotransmitters on the growth of glioblastoma subtypes

Abstract Glioblastomas are aggressive brain tumors associated with the worst patient prognosis. Neurons play critical roles in modulating the growth of glioblastoma. It has been demonstrated that glutamatergic neurons form bona fide synapses with glioblastoma tumor cells that are critical for tumor cell proliferation and migration. It is less clear whether the activity of other neuronal types influences glioblastoma pathophysiology, especially among the different glioblastoma molecular subtypes. Here, we examined the effects of neurotransmitters on the growth of glioblastoma cells characterized as the classical, proneural and mesenchymal subtypes. Patient-derived glioblastoma cell lines were exposed to varying concentrations of different neurotransmitters for 72 hours and assessed for cell viability using the CCK-8 assay. RESULTS: from the CCK8 assay indicate that acetylcholine and dopamine increase glioblastoma cell growth. Consistent with previous findings, we observed an increase in cell viability in all cell lines after being incubated with L-glutamate. The classical subtype has a stronger growth response to L-glutamate compared to the other two subtypes. Transcriptomic data from TCGA showed that the expression of GRIK4 (glutamate ionotropic receptor kainate type subunit 4) is the highest in the classical subtype. By comparing GRIK4 expression with patient survival in TCGA glioblastoma cases stratified by molecular subtypes, we found that high GRIK4 expression correlates with worse prognosis in the classical subtype, but not the proneural or mesenchymal patient groups. Our findings suggest that each glioblastoma subtype may differentially leverage neuromodulatory mechanisms to support their own growth. Ongoing studies are investigating the differential neuronal responses in glioblastoma subtypes using both pharmacological and genetic approaches.