HPSE and neoplasm: Degradation of ECM is mediated by multiple proteases including MMPs, ADAMs, and ADAM-TS (short for a disintegrin and metalloproteinase, and a disintegrin and metalloproteinase with thrombospondin motifs), in addition to heparanase, liberating pro-angiogenic factors that in turn activate angiogenesis and promote the proliferation of tumor cells (185, 187).