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Figure 1. GBM tumor microenvironment. The abnormal neovascularization, due to uncontrolled tumor growth, leads to poor oxygen diffusion and hypoxic regions in the tumor mass, promoting the expression of HIF-1α. This mediator of hypoxia is responsible for the regulation of various processes, including angiogenesis, by enhancing the levels of VEGF that, in turn, act as an inducer of mitogenesis and migration of endothelial cells. This process leads to “cyclic hypoxia” characterized by a dynamic phase of hypoxia and reoxygenation within the tumor mass. Moreover, HIFs have been shown to promote EXOs biogenesis and secretion, promoting cancer metastasis and therapy resistance by mediating both the migration of glioma cells and the proliferation and migration of endothelial cells. Figure was created with
