Vascular Transdifferentiation in the CNS: A Focus on Neural and Glioblastoma Stem-Like Cells

Figure 2

Schematic representation of the glioblastoma perivascular niche and the currently known mechanisms of GSC vascular transdifferentiation. GSCs closely interact with blood vessels in a complex perivascular niche. A close interaction with endothelial cells favors GSC self-renewal and maintenance; and in return GSCs promote neovascularization via several processes. GSCs also constitute the source of proliferating glioblastoma cells which show phenotypical heterogeneity. The tumor is also in close contact with local immune cells (microglia). Vascular transdifferentiation of GSCs into endothelial-like cells is induced via transcriptional regulation of LMO2 and also activation of Tie2 receptor. Transdifferentiation in pericyte-like cells is controlled by Notch1, TGFβ, Flk-1, and SDF1-CXCR4 pathways. Consequently, these tightly controlled mechanisms ensure glioblastoma growth as well as tumor-associated neovascularization.