Role of Angiogenesis and Its Biomarkers in Development of Targeted Tumor Therapies

Figure 3

Mechanism of angiogenesis in cancer. Hypoxia induces the expression of hypoxia inducible factor (HIF), which consequently releases proangiogenic factors, such as VEGF, and upregulates the expression of protease, which leads to basement membrane degradation and pericytes detachment. Furthermore, specialized ECs migrate along the angiogenic factor gradient and differentiate into highly proliferative stalk cells, which initiate the formation of new vessels. PGDF stimulation promotes the attachment of pericytes with reduced proliferation and VEGF sensitivity. VEGF stimulates DLL4 secretion, which binds to Notch-1 receptors, downregulates VEGFR, and suppresses proliferation. Blood supply stimulates further tumor growth.