Vascular endothelial growth factor C (VEGF-C) (VEGF-C)

Vascular endothelial growth factor C (VEGF-C) is a critical signaling protein belonging to the PDGF/VEGF family, primarily responsible for regulating lymphangiogenesis and, to a lesser extent, angiogenesis (UniProt P49767). It functions by binding to its cognate receptors, VEGFR-3 (Flt4) and VEGFR-2 (KDR), following proteolytic activation by enzymes like plasmin or ADAMTS3 (PubMed: 24030867). In healthy physiology, VEGF-C is essential for the development and maintenance of the lymphatic system, ensuring proper fluid homeostasis and immune cell transport (PubMed: 10833153). However, in pathological contexts such as oncology, tumor-derived VEGF-C promotes the formation of peritumoral lymphatic vessels, which serves as a primary route for lymph node metastasis (PubMed: 11242102). Consequently, the VEGF-C/VEGFR-3 axis has become a significant therapeutic target, with drug development focusing on monoclonal antibodies to sequester the ligand or small-molecule tyrosine kinase inhibitors to block receptor signaling (PubMed: 22431502). While targeting this pathway shows promise in limiting cancer spread, safety concerns include potential disruptions to wound healing and the risk of inducing lymphedema in non-target tissues (PubMed: 21460870).

Other names

VEGFCVascular endothelial growth factor-related proteinVRPFlt4 ligand

Inhibition of VEGF-C binding to its receptors (VEGFR-2 and VEGFR-3) or inhibition of the downstream receptor tyrosine kinase activity to block lymphangiogenic and angiogenic signaling (PubMed: 22431502, PubMed: 24030867).