fig1

Figure 1. Steps of angiogenesis. (A) The hypoxic tumour core induces the production of hypoxia-inducible factor-1 and the consequent release of pro-angiogenic factors from tumour cells. (B) Hypoxia upregulates matrix metalloproteinase production, leading to basement membrane and perivascular extracellular matrix degradation. (C) Pro-angiogenic factors activate the endothelial cells of adjacent vessels, and a tip cell migrates along the angiogenic factor gradient. (D) This tip cell is followed by highly proliferative stalk cells, which form the new vascular tubule. (E) Platelet-derived growth factor stimulates the recruitment of pericytes and smooth muscle cells (not shown here) and the vessel matures, allowing for blood flow that stimulates further tumour growth. VEGF: Vascular endothelial growth factor; FGF: fibroblast growth factor; EGF: epidermal growth factor; MMP: matrix metalloproteinase; PDGF: platelet-derived growth factor; PDGFR: platelet-derived growth factor receptor.