Vascular endothelial growth factor C (VEGF-C) is a homodimeric ligand of VEGF R3/Flt-4 and is synthesized with N- and C-terminal propeptides. Fully processed VEGF-C containing only the VEGF homology domain can additionally bind and activate VEGF R2/KDR/Flk-1. VEGF-C interactions with VEGF R3 are critical for lymphangiogenesis. Both the ligand and receptor are usually co-expressed at sites of lymphatic vessel sprouting, in the embryo, and in various pathological conditions. Over-expression of VEGF-C in tumor cells induces tumoral lymphatic hyperplasia, neoangiogenesis, and vessel sprouting, resulting in enhanced lymph flow and metastasis to regional lymph nodes.