Abstract
Matrix metalloproteinases (MMPs), the entities responsible for eradicating the structure of extracellular matrix - ECM, are the zinc or calcium ion-dependent enzymes. This family of enzymes embodies a vast spectrum of proteases ranging from collagenases, stromelysins to the membrane type MMPs. The tasks linked with these enzymes are significant not only for a sound and stable development of the body but are also found guilty of carrying out angiogenesis, promoting tumor development and thus providing means to disseminate the cancer cells to the sites other than the primary tumor locale. At each step of angiogenesis, MMPs are operating, thereby featuring endothelial cells and several growth factors like VEGF, FGF, etc. Activation of pro-MMP2 with the involvement of MT1-MMP is one of the key steps that lead to the synthesis of blood vessels from an already existing one. For limiting the action of MMPs, various therapeutic techniques highlighting the mechanism of MMP inhibition have been studied. Several agents have been investigated for phase I, II and III clinical trials in combination with other anti-cancer therapies. Natural endogenous inhibitors of MMPs, TIMPs have a limited half-life and are thus not suitable for the desired outcome. Synthetic agents like Marimastat and BMS-275291 have shown reliable results. Nonetheless, explicit research is required for novel agents being designed and synthesized to attenuate the activity of matrix metalloproteinases that are accountable for cancer metastasis.
Highlights
The extracellular matrix is likely to undergo degeneration from time to time in order to carry out the crucial processes like tissue repair and remodeling, development of certain components, morphogenesis and assorted signaling activities [1,2]
The discovery of matrix metalloproteinases (MMPs) was based on the fact that for the process of degeneration to take place within the collagen present in the tail of a tadpole, a collagenase activity was required during metamorphosis [4]
First characterized about fifty years ago [5], the matrix metalloproteinases (MMPs), known as matrixins, are a family of endopeptidases that target the molecules of ECM to conduct important physiological activities like wound healing, apoptosis, cell migration, angiogenesis, ovulation, embryonic development, invasion and proliferation [6]
Summary
The extracellular matrix is likely to undergo degeneration from time to time in order to carry out the crucial processes like tissue repair and remodeling, development of certain components, morphogenesis and assorted signaling activities [1,2]. First characterized about fifty years ago [5], the matrix metalloproteinases (MMPs), known as matrixins, are a family of endopeptidases that target the molecules of ECM to conduct important physiological activities like wound healing, apoptosis, cell migration, angiogenesis, ovulation, embryonic development, invasion and proliferation [6] These enzymes have shared structural and functional sites that are preserved among the various members of the family (Figure 1) and are activated by common processes that work at a neutral pH. The general features on the basis of which a proteinase is assessed before designating it as an MMP are sequence similarity with that of collagenase 1 (MMP1), the factor found in the pro-peptide that is responsible for maintaining the matrix metalloproteinases in a zymogen form, the cysteine-switch motif (PRCGXPD), and a catalytic domain comprising of a zinc ion binding motif (HEXGHXXGXXH) [2]. Apart from these substrates, collagenases can act on several other molecules as well that may or may not belong to the Enzyme (Alternative names)
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