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ECM components are degraded by matrix-degrading enzymes, including heparanase, cathepsins, hyaluronidases, matriptases, various serine and threonine proteases (Roycik et al., 2009), and the large superfamily of metzincins, which includes ADAMs (a disintegrin and metalloproteinases), ADAMTSs (ADAMs with thrombospondin motifs), and matrix metalloproteases (MMPs) and their inhibitors [tissue inhibitor of MMPs (TIMPs)] (Mott and Werb, 2004)