VEGF-121, an abundant splicing isoform of vascular endothelial growth factor （VEGF）, exists as a disulfide-linked homodimer. It induces proliferation and migration of vascular endothelial cells, and is essential for both physiological and pathological angiogenesis. Contrast to other isoforms, VEGF-121 has very little affinity for heparin-sulfate proteoglycans, without recruiting Neuropilin1-expressing monocytes （NEMs）, conferring to VEGF-121 the ability to diffuse freely, and increase tumor growth rate in vivo.