MMP9 and neoplasm: On the other hand, overgrowth of tumor or angiogenesis inhibitors produces a hypoxia microenvironment, which is an important feature of rapidly proliferating malignant tumors, induces the upregulation of hypoxia-inducible factor 1 (HIF-1) and its target genes, including vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and MMP-9, and thereby promotes VM formation and increased tumor invasion and metastasis ability [6–11].