Metabolic changes in a zebrafish model of glioblastoma (GBM) led to increased glycolysis and lactate transport and sensing. (A) Schematic representation of the genetic components of the zebrafish GBM model (Mayrhofer et al., 2017). (B) Increased expression of several members of the glycolytic pathway in GBM. Heatmap representing 29 glycolysis genes and their relative expression levels. (C) Analysis of mitochondrial metabolism (acute Mito Stress test) of tumor cells with the Seahorse XP technology. Each experiment was performed in triplicate and normalized to the number of cells. (D) Increased levels of HCAR1 in tumors vs. control as visualized by immunofluorescence. Staining as detailed in the figures, which are representative of at least three different experiments. (E) Gene expression analysis through quantitative PCR (qPCR) expressed as fold changes compared to controls, at 5 days post-fertilization and in adult tumors. Values represent the mean ± SEM of experiments performed in triplicate. P-values <0.05 were considered as statistically significant (*p < 0.05 vs. controls). (F) Whole-mount immunofluorescence of Ph3 proliferating cells in controls and in HRAS-overexpressing larvae treated or not with 20 mM lactate. Green fluorescence represents tumoral cells expressing eGFP-HRASG12V. (G) Number of proliferating cells in the brains treated as indicated.
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