VEGFR1 for Lymphangiogenesis

Abstract

The lymphatic vascular system is a conduit for interstitial fluid extravasated from blood vessels and also plays important roles in maintaining immune responses, lipid uptake, and tissue homeostasis. In recent years, much attention has been given to lymphangiogenesis, a formation of new lymphatic vessels, because lymphangiogenesis has been shown to be involved in lymph node metastasis of tumors.1 See accompanying article on page 658 The development of blood and lymphatic vascular systems is primarily regulated by vascular endothelial growth factor (VEGF) family members. This family consists of 5 members: VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF). There are 3 members of VEGF receptor (VEGFR) tyrosine kinases: VEGFR1, VEGFR2, and VEGFR3. Members of the VEGF family show different affinities for these receptors. VEGFR1 is able to bind VEGF-A, VEGF-B, and PlGF. VEGFR2 is activated primarily by VEGF-A, but cleaved forms of VEGF-C and VEGF-D may also activate this receptor. VEGFR3 is activated by VEGF-C and VEGF-D. Vascular endothelial cells (ECs) express VEGFR1 and VEGFR2, whereas lymphatic ECs express VEGFR2 and VEGFR3 in the adult. The most important molecule in the VEGF family that controls angiogenesis is VEGF-A, and VEGFR2 is the major mediator of VEGF-A driven responses in vascular ECs. VEGFR1, on the other hand, has a higher affinity for VEGF-A …