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A family of secreted proteins (TIMP-1; TIMP-2; and TIMP-3) that play a crucial role in regulating the activity of the secreted METALLOENDOPEPTIDASES (COLLAGENASES; stromelysins, GELATINASES). Of the three characterized, only TIMP-1 and TIMP-2 appear to have related primary structures and inhibitory properties. They influence the activation of the prometalloproteinase and act to modulate proteolysis of extracellular matrix, notably during tissue remodeling and inflammatory processes. On certain cell types, they can exhibit growth factor-like activity, and they can inhibit the tumorigenic and metastatic phenotype in cancer cells. (Pharmacol Ther 1993;59:329-41)