Heparanase enhances shedding of syndecan-1 and high levels of heparanase and shed syndecan-1 in the tumor microenvironment are associated with elevated angiogenesis and poor prognosis in myeloma, by activating integrin and VEGF receptors on adjacent endothelial cells thereby stimulating tumor angiogenesis (80, 81). This evidence concerns the gene HPSE and neoplasm.