VEGFA and cancer: Some investigations have described that hypoxia, via hypoxia-inducible factor-1 (HIF-1), enhances the expression of proangiogenic factors such as VEGF, Ang-1 and Ang-2 in endothelial and cancer cells (139, 140), and promotes the synthesis of CXCR4 (a receptor for CXCL12) and Tie2 (angiopoietin receptor) on macrophages, which allows the interstitial migration of proangiogenic macrophages inside the tumor (128, 141, 142).