Inhibition of heparanase-mediated degradation of extracellular matrix heparan sulfate by non-anticoagulant heparin species.

摘要: Incubation of human platelets, neutrophils, or highly metastatic mouse lymphoma cells with sulfate-labeled extracellular matrix (ECM) results in heparanase-mediated release labeled heparan sulfate cleavage fragments (0.5 less than Kav 0.85 on Sepharose 6B). This degradation was inhibited by native heparin both when brought about intact their released heparanase activity. Degradation ECM may facilitate invasion normal and malignant through basement membranes. The present study tested the inhibitory effect nonanticoagulant species that might be potential use preventing mediated extravasation bloodborne cells. For this purpose, we prepared various low-sulfated low-mol-wt heparins, all which exhibited 7% anticoagulant activity heparin. N-sulfate groups are necessary for its but can substituted an acetyl group provided O-sulfate retained. could removed N positions were resulfated. Total desulfation abolished Heparan a 25-fold potent inhibitor Efficiency heparins to inhibit decreased main molecular size, synthetic pentasaccharide, representing binding site antithrombin III, devoid Similar obtained activities from We propose inhibiting interfere dissemination tumor development experimental autoimmune diseases.