Fig. 3: Mesenchymal GBMs are enriched in surface HA receptors, and show HA/TMZ synergy on cell motility.

a Genes belonging to the “HA binding” GO term (GO:0005540, from The Gene Ontology Resource) grouped according to where they act: cell surface vs. matrix (extracellular). Left. Heatmap of LOG10 expression (normalized read counts) for each gene. Right. Pearson correlation analysis of the molecular stratification signatures (as in Fig. 1) and the HA binding gene sets (surface HA binding and matrix HA binding). R value is shown in each square, * p-value of the correlation<0.05. Bottom. Graphical summary: mesenchymal GBM are enriched in genes coding for cell surface HA-binding proteins, and proneural GBM in genes coding for matrix HA-binding proteins. b Left. Scratch wound assay: cell migration (Relative Wound Density, RWD, %) data as a function of time, +/− 20 µM TMZ treatment and +/− 0.25/mL HA (mean ± SEM of n = 6 wells per condition); Right. RWD % data were fitted as \({RWD}=a* (1-{e}^{-{bt}})\), where \(a\) and \(b\) are respectively the max wound closure and the wound closure rate; in this graph, the overall migration speed was calculated as \(V=a* {b}\) (RWD/time) and normalized against controls without TMZ (non-normalized \(V\) values are reported in Supplementary Fig. S6) to obtain a relative migration speed (in the plot: V ± Standard Error as obtained from the fitting; two-tailed unpaired t-test, ***p < 0.005).