TIMP-1, TIMP-2, TIMP-3 and TIMP-4 (for tissue inhibitor of metalloproteinases -1, -2, -3 and -4) complex with metalloproteinases such as collagenases, gelatinases and stromelysins, resulting in irreversible inactivation of the metalloproteinase. TIMP-1 is identical to EPA (erythroid-potentiation activity). PTH has been shown to be a regulator of TIMP-2 in osteoblastic cells. TIMP-3 may be involved in regulating trophoblastic invasion of the uterus as well as in regulating remodeling of the extracellular matrix during the folding of epithelia, and in the formation, branching and expansion of epithelial tubes. TIMP-4 is most highly expressed in heart tissues. Studies have demonstrated that TIMP1 is useful as a biomarker for early detection of colorectal cancer, outperforming CEA. Additionally, TIMP1 studies have demonstrated its role in CRC tumorigenesis, as well as observing its overexpression in metastatic lymph nodes.
