Considering that Ang-1 secreted from astrocytes stimulates physiological angiogenesis under hypoxic conditions (see Section 3.3), it is possible to suggest that Ang-1 released by astrocytes and glioma cells acts in a coordinated manner activating Tie-2 signaling in ECs to promote the highly vascularized phenotype of glioblastoma, and at least part of the signaling depends on AEG-1 and HIF-1, permitting the transition since a glioma tumor (less aggressive) to glioblastoma (highly aggressive). Here, HIF1A is linked to central nervous system cancer.