1991 Volume 3 Issue 10 Pages 82-90
Extravasation of normal and malignant blood-borne cells correlates with degradation of heparan sulfate (HS) in the subendothelial extracellular matrix (ECM). This degradation is brought about by an endo-β-D-glucuronidase (heparanase) that cleaves HS at specific intrachain sites. Heparanase mediated degradation of the ECM'HS was stimulated by plasminogen activator and inhibited by native heparin and by various modified and low molecular weight non-anticoagulant species of heparin. These heparin also inhibited the incidence of tumor metastasis and the severity of autoimmune diseases in experimental animals. The angiogenic factor, basic fibroblast growth factor (bFGF) has been identified in basement membranes of diverse tissues such as the cornea and blood vessels, suggesting that ECM may serve as a storage depot for bFGF. Exposure of ECM to heparanase resulted in release of active bFGF, both in vitro and in vivo. Likewise, intact cells utilized their heparanase activity to release this potent endothelial cell growth factor from ECM. Heparanase mediated degradation of the ECM-HS may thus function in both cell invasion and neovascularization in normal and pathological situations. We propose that storage of endothelial cell growth factors in ECM may provide a novel mechanism for regulation of capillary blood vessel growth. Under normal conditions it may prevent them from acting on the vascular endothelium, while perturbation of the ECM may elicit localized endothelial cell proliferation and neovascularization.
