Matrix Metalloproteinases

The matrix metalloproteinases (MMPs) are a family of endopeptidases that play a key role in maintaining the balance between deposition and degradation of extracellular matrix. Activity of MMP-2 and MMP-9 is associated with tumor progression and metastasis in many cancers, presumably facilitating the invasion of tumor cells and sprouting of new vasculature (Overall and Lopez-Otin 2002). Consistent with these functions, inhibitors of MMPs have been shown to suppress both tumor invasion and angiogenesis. In neuroblastoma, an association between increased levels of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in patients with advanced stage has been reported (Ribatti et al. 2001; Sugiura et al. 1998). In addition, decreased expression of the tissue inhibitor metalloproteinase TIMP-2, a specific inhibitor of MMP-2 and MMP-9, has been significantly related to advanced disease (Ara et al. 1998). Lastly, Sakakibara et al. have demonstrated that higher ratios of gelatinase activation resulting from high expression of membrane-type matrix metalloproteinase-1 (MT-MMP-1) is associated with stage-IV disease and unfavorable outcome (Sakakibara et al. 1999).

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