Matrix Metalloproteinase (MMP) Inhibitors & Substrates

Matrix metalloproteinases (MMPs) is an enzyme that decomposes extracellular matrix (ECM) proteins. They play an important role in both normal and diseased cells. Proteases plays an important role in many diseases. Extracellular protein hydrolase is the material required for the passage of tumor cells. Hydrolyzing ECM protein is necessary for the migration of invasive tumor. In addition, vascular hyperplasia, which supports tumor growth, also hydrolyzes ECM protein by invading epidermal cells. There are four kinds of endopeptidases: serine protease, cystine protease, aspartyl protease, substrate attribute protease, all of which are related to the development and migration of more than one tumor. MMPs is the most important of the four proteases in the development of tumor.

Types of MMPs

• There are three kinds of gelatinase typeⅠ: interspace zymogenase, neutrophil collagenase and collagenase, all of which can decompose typeⅠ,Ⅱand Ⅲ types of fibrillar collagens.
• TypeⅡ contains two kinds of 72kDa, 92kDa gelatinases and metalloelastase, which can decompose type Ⅳ andⅤbasal lamina non-maintenance collagen, It can also decompose type VII collagen and fibronectin, X short chained collagen, elastic protein and gold attribute protease .
• Type Ⅲ is composed of stromelysin-1, lysin-2 and matrilysin, which can decompose proteoglycan, binding protein and laminin in type Ⅳ and type X collagen.
• MRNA in situ hybridization confirmed that lysin-3 is very important for malignant diseases, and its proteolytic function has been described. Membrane-type metalloproteinases (MT-MMP) have been found, MT-MMP can be combined on the cell membrane is there, MT-MMP is a special activate progelatinase A. Since its initial discovery, the genes of MT-MMP have been identified, and these enzymes are temporarily in type Ⅳ of MMP.

The role of MMPs in tumor

The decomposition ability of MMPs is related to the time of enzyme secretion and inhibitor, which includes general blood protease inhibitors, such as a2-macroglobulin, as well as special inhibitors, such as TIMP-1, TIMP-2, and TIMP-3. A number of diseases, such as inflammation, sclerosis, and cancer, are associated with imbalances between enzymes and inhibitors, which cause extracellular matrix to break down. Studies have shown that the force of MMP in the process of cancer development will be greater than the inhibition of the agent, MMP helps the proliferation and aggression of the first grade tumor, the cells of the tumor to pass through the vascular cell wall, and the growth and invasion of the second stage tumor. In addition, MMP also helps to promote the proliferation and invasion of the first grade tumor, the cell wall of the blood vessel, and the growth and invasion of the second stage tumor.

References

1. Morrison, C. J., Butler, G. S., Rodríguez, D., & Overall, C. M. (2009). Matrix metalloproteinase proteomics: substrates, targets, and therapy. Current opinion in cell biology, 21(5), 645-653.
2. Radisky, E. S., Raeeszadeh‐Sarmazdeh, M., & Radisky, D. C. (2017). Therapeutic potential of matrix metalloproteinase inhibition in breast cancer. Journal of cellular biochemistry, 118(11), 3531-354