Establishment of human glioblastoma cell culture collection

Background/Objectives: Glioblastoma (GBM) is the most aggressive type of primary brain cancer, affecting children and adults alike and is associated with a poor prognosis (less than 15 months). It is therefore critical to develop more effective therapies that improve survival and reduce side effects for these lethal brain cancers. Glioblastoma cells constantly reprogram their metabolism to adapt to changing conditions. As current treatments are not effective, the need for a deeper understanding of metabolic processes and signaling pathways grows critical. Methods: To support this, we have established a collection of human GBM cell cultures derived from freshly resected tumor tissues from 78 patients undergoing surgery at CHU de Quebec, Laval University. We aimed to characterize this cell lines by combining histologic, metabolomic and gene expression analysis. Results: Among the 21 cases that successfully generated cell lines, all were IDH-wildtype (IDH-wt) GBMs, with molecular profiles, including Ki-67 proliferation index, ATRX status, p53 expression, and MGMT promoter methylation. Characterization of five cell lines revealed significant metabolic and phenotypic heterogeneity, with differences in amino acid levels, TCA cycle metabolites, and RNA expression of GBM subtype markers. Our data suggest that mesenchymal-like GBM cells exhibit higher metabolic activity compared to proneural-like cells. Conclusions: Together, the analyses highlight the heterogeneity of GBM cells across patients. These findings emphasize the complexity of GBM and the need for personalized approaches in treatment, taking into account the diverse metabolic and molecular characteristics of GBM cells.