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

Vascular endothelial growth factors C and D are secreted protein ligands that together form a distinct subfamily within the VEGF family. Both are primarily responsible for lymphangiogenesis and signal through VEGFR-3 (Flt4) and VEGFR-2 (Kdr/Flk1) on endothelial cells, driving proliferation and remodeling of lymphatic and, to a lesser extent, blood vessels. Structural and processing similarities underlie their dual receptor specificity. Their activity is critical for normal lymphatic development, but overexpression or dysregulation is implicated in tumor metastasis, tissue repair, and lymphatic disease. Therapeutically, targeting VEGF-C/D–VEGFR-3 signaling is under exploration for cancer, lymphedema, and other lymphatic disorders, where suppression of aberrant lymphangiogenesis may be beneficial, but with safety concerns related to compromised physiological vascular function.

Other names

Flt4 ligandLymphatic growth factor Cc-fos-induced growth factor (FIGF)Lymphatic growth factor D

Inhibition: Drugs/traps/antibodies block binding of VEGF-C or VEGF-D to VEGFR-2 or VEGFR-3, preventing signal transduction necessary for lymphangiogenesis and angiogenesis. Downstream, blockade reduces lymphatic vessel formation, tumor spread via lymphatics, and tissue edema in susceptible disease settings.