VEGFA and central nervous system cancer: c-MET upregulation itself may be a key factor contributing to resistance to angiogenic agents in gliomas.15,16 HIF-1a may accomplish this at least in part by recruiting bone marrow derived cells that in turn express matrix metalloproteinase 9 (MMP-9).17 MMP-9 is a critical downstream factor of HIF-1a that enables the angiogenic switch by making sequestered VEGF bioavailable for its receptor VEGFR2.18–20 Similarly, MMP-9 deficiency impedes neovascularization in glioblastoma due to the inability of VEGF to bind to its receptor.21