Fig. 4: Both perivascular and network glioma cells are particularly resilient.
From: Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma
a Analysis of fractions of cells with different number of TMs (S24 glioblastoma stem-like cells (GBMSCs), D41, n = 4 regions in 3 mice, 52–104 cells, two-tailed t-tests). b Analysis of the connectivity of cells in the perivascular and parenchymal compartment (S24 GBMSCs, D65 ± 4, n = 10 regions in 6 mice, 148–259 cells, two-tailed t-tests). c Ratio of tumor cell counts in the same regions 7 days after and before sham treatment or irradiation (RTx) (S24 GBMSCs, n = 5 regions in 3 mice per group, one-way ANOVA (p = 0.0002), Tukey’s post hoc test). d Representative 2-PM images of the same tumor region before and 7 days after radiotherapy demonstrate that perivascular glioma cells are largely radioresistant (S24 GBMSCs). Arrows: disappearing parenchymal tumor cells. Arrowheads: surviving perivascular tumor cells. e Ratio of tumor cell counts in the same regions 7 days after and before sham treatment or irradiation (RTx) categorized by connectivity and compartment (S24 GBMSCs, n = 5 regions in 3 mice per group, one-way ANOVA (p = 1.55; × 10−6), Student–Newman–Keuls post hoc test). The analysis revealed that non-connected tumor cells in the parenchyma are most susceptible for the cytotoxic effects of radiotherapy. In contrast, non-connected cells in the PVN are more radioresistant, thereby demonstrating the protective environment promoted by the PVN. In the PVN, interconnection has an additive effect on radioresistance. f Left: Ratio of cell counts of S24 GBMSCs in the same regions 21 days after and before temozolomide or sham treatment (n = 5 regions in 3 mice per group, one-way ANOVA on ranks (p = 0.0018), Student–Newman–Keuls post hoc test). Right: Exemplary 2-PM images before and 21 days after temozolomide treatment in S24 GBMSCs. Arrowheads: surviving perivascular GBMSCs. g Ratio of cell counts of T269 GBMSCs in the same regions 21 days after and before temozolomide or sham treatment (n = 5 regions in 3 mice per group, one-way ANOVA on ranks (p = 0.0002), Student–Newman–Keuls post hoc test). Data a–c, e–g are represented as mean + SEM. *p < 0.05, **p < 0.01, ***p < 0.001, n.s. = not significant. Source data are provided as a Source Data file.
