What Is Matrix Metalloproteinase 3?

Matrix metalloproteinase 3, also known as stromelysin-1, is an enzyme that helps to degrade the extracellular matrix. Such degradations occur during normal functioning, such as when tissues are reorganized. They can also take place in response to disease; for example, when tumor cells metastasize.

Like other matrix metalloproteinases (MMPs), matrix metalloproteinase 3 comes from the MMP gene cluster. It is encoded by the MMP3 gene. When this gene is expressed, the enzyme is actually secreted in an inactive form. Once outside of the cell, enzymes called proteases remove a portion of the enzyme and activate it.

Following activation, matrix metalloproteinase 3 has two main functions. It is capable of breaking down a variety of matrix compounds, including several types of collagen, fibronectin, elastin, and laminin. This enzyme also serves an activation function for other MMPs. Activation of MMP-1, MMP-7, and MMP-9 is performed not by proteases, but by MMP-3 itself.

The dual function of matrix metalloproteinase 3 means that it is an essential component of restructuring connective tissue. Under normal conditions, this enzyme is important in wound repair. In times of disease, however, it can be responsible for the continuation of atherosclerosis, and tumor cell movement.

Evidence suggests that this enzyme is involved in neurodegenerative brain disorders, as well. The release of MMP-3 into the extracellular matrix activates microglia, or "white matter" brain cells. Microglia can induce programmed cell death, known as apoptosis, in neurons. Apoptosis is a facet of many neurodegenerative disorders such as Parkinson's disease, and scientists believe that MMP-3 release is the main signal that begins this process.

Mutations in the MMP3 gene can lead to certain disease states. Some mutations can create more powerful promoter genes, increasing the amount of matrix metalloproteinase 3 produced by cells. Diseases like acute myocardial infarction have been associated with overactivity of MMP-3. Mutations can create less effective promoters as well. Underexpression of the MMP3 gene is involved in cleft lip and cleft palate, as well as coronary atherosclerosis.

The response to chemotherapy in cancer may also be predicted by MMP3 gene mutations. Patients with a form of carcinoma carrying two copies of the MMP3 gene variant coding for a less effective promoter tended to respond well to chemotherapy. Individuals with mixed copies, or two copies coding for the more effective promoter, did not see the same amount of improvement. These variable results may be due to a more effective promoter creating conditions that make it easier for tumor cells to metastasize.