It has been demonstrated that hypoxic GBM cells release small EVs (50–200 nm) with pro-angiogenic capacity, due to their enrichment with hypoxia-induced proteins including matrix metalloproteinase-9 (MMP-9), IL-8, platelet-derived growth factors (PDGFs), insulin-like growth factor binding protein (IGFBP)-1 and -3, and caveolin-1, which are associated with poor prognosis in glioma (94). This evidence concerns the gene MMP9 and central nervous system cancer.