The onset of angiogenesis is believed to be an early event in tumorigenesis and may facilitate tumor progression and metastasis. Several growth factors with angiogenic activity have been described and include fibroblast growth factor (FGF), platelet derived growth factor (PDGF) and vascular endothelial growth factors (VEGFs). The VEGF protein family is comprised of VEGF, VEGF-B, VEGF-C and VEGF-D, all of which may exhibit angiogenic function in vivo. VEGF-B, which exists as two alternatively spliced isoforms known as VEGF-B167 and VEGF-B186, is abundantly expressed in heart and skeletal muscle and is frequently co-expressed with VEGF. VEGF-C binds to and specifically activates Flt-4 and Flk-1.
