Heparanase-mediated release of bioactive molecules sequestered in the ECM. Heparanase cleaves HSPGs (arrows) and releases a variety of physiologically and pathologically important molecules. Inset shows the cleavage site within the antithrombin-binding heparin 3H-octasaccharide. The actual antithrombin-binding sequence corresponds to sugar units 2–6 (within brackets). X in sugar unit 4 represents hydrogen or SO–3. Adapted from Pikas et al. (17).