VEGFA and neoplasm: IGFBPs are high-affinity receptors of IGF, with six subtypes of IGFBP1–6, secreted by endothelial cells living in macro-vessels and capillaries.198 Pro-angiogenic IGFBP2 induces chemotaxis and migration of ECs by increasing VEGF transcription and IGF levels.208,209 IGFBP3 up-regulates the expression of VEGF, MMP2, and MMP9 and promotes tube formation.210 IGFBP4, IGFBP5, and IGFBP6 appear to inhibit angiogenesis indirectly.196 More studies are expected to dissect the roles and mechanisms of IGF family in tumor angiogenesis.