VEGF-C Protein, Human

Vascular endothelial growth factor-C (VEGF-C) is a pivotal member of the VEGF family of polypeptide growth factors, discovered in 1996 as the first specific ligand for VEGFR-3 (Flt-4). Encoded by the VEGFC gene on human chromosome 4q34, VEGF-C is secreted as a preproprotein that undergoes sequential proteolytic processing to generate a mature 21 kDa homodimer. This processing enhances its affinity for VEGFR-3 by ~400-fold and enables binding to VEGFR-2 (KDR), the primary VEGF-A receptor. The processed VEGF-C also interacts with neuropilin-2 (NRP-2), facilitating co-receptor function. VEGF-C is expressed in various human tissues, including heart, skeletal muscle, and vascular smooth muscle cells, with particularly high levels in malignant tumors. Physiologically, VEGF-C serves as the master regulator of lymphatic system development, promoting proliferation, migration, and survival of lymphatic endothelial cells during embryogenesis and adult tissue remodeling. In pathological contexts, VEGF-C induces lymphangiogenesis in tumors, inflammatory lesions, and fibrotic tissues.