, the formation of blood vessels, occurs in a coordinated series of steps, which can be divided into a destabilization, a proliferation, and a maturation phase.
Extensive studies have revealed a variety factors involved in neoangiogenesis, the main protagonists are: Vascular endothelial Growth Factor (VEGF), basic Fibroblast Growth Factor (bFGF), various members of the Transforming Growth factor beta (TGFβ) family and hypoxia (Hypoxia-inducible transcription factor, HIF)... Other factors that have angiogenic properties include the angiopoietins, (Ang-1); hepatocyte growth factor (HGF); Platelet-derived growth factor (PDGF-BB); Insulin-like growth factor family (IGF-1, IGF-2) and the Neurotrophins (NGF).
One of earliest events in angiogenesis is the degradation of the vascular basement membrane and the remodeling of the extracellular matrix (ECM). Several matrix metalloproteinases (MMPs), including MMP-2, -3, and -9 play an important role in this system, and are associated with tumor progression, including invasion, metastasis, growth, migration, and angiogenesis.
Integrins are the principle adhesion receptors used by endothelial cells to interact with the extracellular environment and are necessary for cell migration, proliferation, and survival.