Figure 2.

Tumor angiogenesis. Hypoxia within the tumor induces the release of different pro-angiogenic factors, such as VEGFs, EGF, FGF, IGF1 or TGFB1. VEGF-A is the major angiogenic activator and it induces angiogenesis upon binding to VEGFR2, mainly expressed by tumor endothelial cells. The new blood vessels allow exchange of oxygen, nutrients and waste products, leading to tumor growth and proliferation. Moreover, once cancer cells acquire a more invasive phenotype, they can intravasate into blood vessels and reach distant locations leading to metastasis. Disseminated tumor cells that have spread to a secondary site can enter a state of metastatic dormancy or induce angiogenesis and start proliferating.