• Tumor-derived HIF→ ↑endothelial cell sprouting via PDGF, EGF, VEGF, FGF, Ang2, IL-8→ ↑endothelial cell migration→ support nutrient and metabolite to tumor cells • ↓ICAM-1, VCAM on endotheleial cells→ ↓immune cell infiltration • ↑TGF-β, BMP in TME convert endothelial cells to CAF. This evidence concerns the gene EGF and neoplasm.