TIMP-3 ELISA Kit, Human

The TIMP-3 polypeptide sequence is 37% and 42% similar to the sequences of TIMP-1 and TIMP-2, respectively. The TIMP-3 protein has 188 amino acids. It has a conserved glycosylation site near the C-terminus. Characterisation of the human recombinant TIMP-3 reveals that it has both a 27 kDa glycosylated and a 24 kDa unglycosylated species. Unlike the other TIMPs, which are soluble, TIMP-3 is unique in being a component of extracellular matrix (ECM). TIMP-3 is localised to the ECM in both its glycosylated and unglycosylated forms. In addition, TIMP-3 is the only TIMP to inhibit members of the ADAM (a disintegrin and metalloprotease domain) family such as tumor necrosis factor-alpha-converting enzyme; this may account for its ability to induce apoptosis. It is the only TIMP to inhibit shedding of L-selectin and interleukin-6 receptors. Moreover, TIMP-3 is the only TIMP directly implicated in a disease process: Ser-Cys mutants of TIMP-3 accumulate in Bruch’s membrane of the eye and cause Sorsby’s fundus dystrophy. TIMP-3 also promotes the detachment of transformed cells from the ECM and is involved in the formation, branching, and expansion of epithelial tubes and in regulating trophoblast invasion of the uterus.² Mutations in the human TIMP-3 gene cause a dominantly inherited, adult-onset blindness (Sorsby’s fundus dystrophy or SFD).³ It was demonstrated that increased expression of TIMP-3 resulted in a statistically significant suppression of tumor growth. Deposition of TIMP-3 in the surrounding ECM by tumor cells may inhibit tumor growth by preventing local expansion of tumor, retarding the release of growth factors sequestered in ECM, or inhibiting angiogenesis. TIMP-3 over-expression had no effect on the growth of the two tumor cell lines in vitro. Because recombinant TIMP-3 inhibits endothelial cell migration and tube formation in response to angiogenic factors, thus, the effect of TIMP-3 on tumor growth seen in this study may be a consequence of its angiostatic action.⁴