Chemotherapeutic Stress Induces Transdifferentiation of Glioblastoma Cells to Endothelial Cells and Promotes Vascular Mimicry

Figure 4

Orthotopic xenograft tumors treated with TMZ exhibit elevated expression of markers of both immature and mature endothelial cells. (a) Athymic nude mice had PDX GBM cells implanted intracranially in the right cerebral hemisphere. Five days later, treatment was initiated, with three groups of mice receiving different doses of TMZ (2.5, 5, or 10 mg/kg, i.p.). Mice treated with DMSO served as a control (, in both male and female mice). Mice were given the drug each day for five consecutive days. Five days after cessation of treatment, mice were sacrificed and brains collected for ex vivo flow cytometry analysis. The inset flow cytometry plot shows how human PDX GBM cells were identified and how mouse cells were excluded, based on CD45 staining. (b) Representative FACS plots from each treatment group showing the percentages of cells positive for CD133, a GSC marker, and CD105, an intermediate endothelial cell marker. (c) Quantification of the CD133⁺ population in each treatment group. (d, e) Quantification of the percentage of human tumor cells positive for both CD133 and (d) CD105 and (e) CD31, markers of endothelial cells. Dots represent means from individual animals. The means of all mice were compared by one-way ANOVA with multiple comparisons. , , . .