MMP-9

Official Full Name

matrix metallopeptidase 9

Organism

Homo sapiens

GeneID

4318

Background

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling. [provided by RefSeq, Jul 2008]

Synonyms

GELB; CLG4B; MMP-9; MANDP2;

Bio Chemical Class

Peptidase

Protein Sequence

MSLWQPLVLVLLVLGCCFAAPRQRQSTLVLFPGDLRTNLTDRQLAEEYLYRYGYTRVAEMRGESKSLGPALLLLQKQLSLPETGELDSATLKAMRTPRCGVPDLGRFQTFEGDLKWHHHNITYWIQNYSEDLPRAVIDDAFARAFALWSAVTPLTFTRVYSRDADIVIQFGVAEHGDGYPFDGKDGLLAHAFPPGPGIQGDAHFDDDELWSLGKGVVVPTRFGNADGAACHFPFIFEGRSYSACTTDGRSDGLPWCSTTANYDTDDRFGFCPSERLYTQDGNADGKPCQFPFIFQGQSYSACTTDGRSDGYRWCATTANYDRDKLFGFCPTRADSTVMGGNSAGELCVFPFTFLGKEYSTCTSEGRGDGRLWCATTSNFDSDKKWGFCPDQGYSLFLVAAHEFGHALGLDHSSVPEALMYPMYRFTEGPPLHKDDVNGIRHLYGPRPEPEPRPPTTTTPQPTAPPTVCPTGPPTVHPSERPTAGPTGPPSAGPTGPPTAGPSTATTVPLSPVDDACNVNIFDAIAEIGNQLYLFKDGKYWRFSEGRGSRPQGPFLIADKWPALPRKLDSVFEERLSKKLFFFSGRQVWVYTGASVLGPRRLDKLGLGADVAQVTGALRSGRGKMLLFSGRRLWRFDVKAQMVDPRSASEVDRMFPGVPLDTHDVFQYREKAYFCQDRFYWRVSSRSELNQVDQVGYVTYDILQCPED

Open

Disease

Brain cancer, Colorectal cancer, Corneal disease, Crohn disease, Hepatitis virus infection, Ischaemic/haemorrhagic stroke, Lung cancer, Renal cell carcinoma, Rheumatoid arthritis, Solid tumour/cancer, Stomach cancer, Ulcerative colitis

Approved Drug

Clinical Trial Drug

7 +

Discontinued Drug

7 +

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Detailed Information

Matrix metalloproteinases (MMPs) are a group of Zn2+ -dependent neutral endopeptidases that have transmembrane transport and secretion functions, which are mainly used to degrade extracellular matrices. MMP-9 is one of the most closely related members of the MMPs family to cerebrovascular. When activated, it can degrade the cerebral vascular basement membrane components, increase the permeability of the blood-brain barrier, and aggravate the occurrence of brain edema. A number of animal experimental models have also confirmed that the high expression of MMP-9 can aggravate the destruction of the blood-brain barrier and promote the occurrence of cerebral edema. Knocking out MMPs in mice or using MMPs inhibitors can alleviate cerebral edema.

Biological Function of MMP-9

In the process of tumor invasion and metastasis, the destruction of ECM is a key process of tumor cell invasion and metastasis. MMP-9 is considered to be an important molecular marker of tumor invasion and metastasis. If its expression is inhibited, the invasion and transfer of MMP-9 may effectively be controlled. MMP-9 promotes tumor invasion and metastasis by: degrading molecular substances of ECM; regulating cell adhesion; decomposing vascular basement membrane and perivascular matrix with other enzymes, which is an important condition for vascular tree growth. Only through degradation process, Endothelial cells can migrate into the surrounding tissues and gradually form vascular trees, promoting the metastasis and invasion of tumor cells.

MMP-9 Figure 1. Schematic illustration about targets of MMP-9 in extracellular environment. (Huang, H. 2018)

As an inflammatory mediator involved in the development of many diseases, MMP-9 regulates inflammatory mediators by regulating physical barriers and forms chemokine gradients in inflammatory tissues to control leukocyte movement to the lesion. Autoimmune diseases involve major cellular and immune systems, and MMP-9 is thought to be involved in this disease state. MMP-9 plays an important role in tissue destruction and remodeling during inflammatory reactions.

MMP-9 and Tumor

In patients with non-small cell lung cancer (NSCLC), elevated MMP-9 levels in the serum and respiratory tract are also common. The study examined MMP-9 in exhaled breath condensate, whole blood, and thoracic exudate in 40 patients with NSCLC and 40 controls in patients with thoracic exudation. MMP-9 levels in exhaled condensate, whole blood, and thoracic exudate were significantly higher in the NSCLC patients than in the control group. MMP-9 is positively associated with exhaled condensate, smoking, and tumor stage. Therefore, MMP-9 in exhaled breath can be used as a non-invasive monitoring tool for lung cancer.

Some studies have found that the levels of MMP-9 in the serum of patients with NSCLC are significantly different from those of benign lung disease group and healthy group. The level of serum MMP-9 increases significantly with tumor volume, lymph node metastasis and clinical stage progression. It is suggested that serum MMP-9 is a good indicator for predicting the status of lung cancer invasion and metastasis, and has more important clinical significance for the diagnosis of NSCLC.

MMP-9 and Cerebrovascular Disease

There is a relationship between the expression level of MMP9 and the hemorrhagic transformation after cerebral ischemia. The high expression level of MMP9 can predict the subsequent hematopoietic transformation, and the later observations show that the level of MMP9 in the plasma of patients with hemorrhagic transformation after cerebral hemorrhage is higher. In addition, MMP9 levels were significantly elevated in patients with hemorrhagic transformation compared with those without hemorrhagic transformation, and MMP9 expression was predictive of ecchymosis in patients with ischemic stroke receiving tPA. Both animal models and clinical studies have shown an increase in MMP9 levels in cerebral ischemia.

References:

Huang, H. (2018). Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances. Sensors, 18(10), 3249.
Merdad, A. , Karim, S. , Schulten, H. J. , Dallol, A. , Buhmeida, A. , & Al-Thubaity, F. , et al. (2014). Expression of matrix metalloproteinases (mmps) in primary human breast cancer: mmp-9 as a potential biomarker for cancer invasion and metastasis. Anticancer research, 34(3), 1355-66.
Abdelnaseer, M. M. , Elfauomy, N. M. , Esmail, E. H. , Kamal, M. M. , & Elsawy, E. H. . (2017). Matrix metalloproteinase-9 and recovery of acute ischemic stroke. Journal of Stroke and Cerebrovascular Diseases, 26(4), 733-740.

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