VEGFC

VEGFC, short for vascular endothelial growth factor C, is a member of the VEGF family and a secreted signaling protein that primarily regulates lymphangiogenesis, the growth of lymphatic vessels, with additional roles in angiogenesis under certain conditions. It is encoded by the VEGFC gene in humans and is expressed in a variety of tissues, including lymphatic endothelium, macrophages, and tumor cells. During development, VEGF-C helps form the lymphatic vasculature, while in adulthood it participates in tissue repair, inflammation, and remodeling of the lymphatic system.

VEGF-C exerts its effects mainly through binding to the VEGF receptors VEGFR-3 (Flt-4) and, to a lesser extent, VEGFR-2 (KDR/Flk-1). Activation of VEGFR-3 promotes lymphatic endothelial cell proliferation, migration, and vessel sprouting. Receptor binding and signaling are enhanced when VEGF-C is proteolytically processed from an inactive precursor to mature forms by proteases such as ADAMTS3; this maturation increases affinity for VEGFR-3 and, in some contexts, allows interaction with VEGFR-2.

Physiological roles include guiding lymphatic vessel development, maintaining lymphatic function, and contributing to wound healing and inflammatory responses. Pathologically, VEGF-C–driven lymphangiogenesis can facilitate tumor metastasis to lymph nodes and contribute to diseases involving the lymphatic system, such as lymphedema. Therapeutically, VEGF-C has been explored to promote lymphatic growth in lymphedema and tissue repair, while strategies to inhibit VEGF-C/VEGFR-3 signaling are studied to limit cancer progression.

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