Heparanases (HPA) degrade heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs) in the extracellular matrix and play animportant role in the extravasation of blood-borne tumor cells and inflammatory leukocytes. HPA1 dismantles the subendothelial basal membrane and facilitates the metastasis of blood-borne tumor cells. Furthermore, HPA1 induces angiogenesis and likely promotes the vascularization of tumors. Upon degradation, HPAs free growth factors and cytokines that stimulate cell proliferation and chemotaxis. Fibroblasts endocytose extracellular HPA1 for cytoplasmic accumulation in vitro. Proteolytic processing at the cell surface of a precursor begets an active form of HPA1.
