MMP7

Matrix metallopeptidase 7 (MMP7), also known as matrilysin or PUMP-1, is an enzyme that in humans is encoded by the MMP7 gene located on chromosome 11. This enzyme belongs to the matrix metalloproteinase (MMP) family, a diverse group of peptidases involved in the breakdown of extracellular matrix components. MMP7 plays a crucial role in various physiological processes, including embryonic development, reproduction, and tissue remodeling. However, its aberrant expression is associated with several pathological conditions, particularly cancer.

Function

MMP7 is unique among MMPs due to its broad substrate specificity and its ability to degrade several components of the extracellular matrix (ECM), such as elastin, fibronectin, and laminin. Unlike most MMPs, MMP7 is secreted as an active enzyme rather than a zymogen. This characteristic allows MMP7 to participate actively in immediate cellular responses to environmental changes. Its activities are implicated in processes such as wound healing, angiogenesis, and the epithelial-mesenchymal transition (EMT), which are critical in both normal physiology and disease progression.

Gene and Expression

The MMP7 gene is regulated by various factors, including cytokines, growth factors, and cell-cell and cell-matrix interactions. Its expression is typically low in normal tissues but can be upregulated in certain pathological conditions, such as inflammation and cancer. In tumors, MMP7 is often overexpressed in cancer cells and surrounding stromal cells, contributing to tumor invasion and metastasis by degrading ECM barriers and facilitating cancer cell migration.

Clinical Significance

The role of MMP7 in cancer has been extensively studied, with evidence suggesting its involvement in the progression of colorectal, breast, gastric, and pancreatic cancers, among others. MMP7 facilitates tumor growth and spread by not only degrading ECM components but also by activating other proteases, modulating cell adhesion molecules, and influencing tumor angiogenesis. Consequently, MMP7 has been investigated as a potential biomarker for cancer diagnosis and prognosis, as well as a target for therapeutic intervention.

In addition to its role in cancer, MMP7 has been implicated in other diseases characterized by excessive or aberrant ECM remodeling, such as pulmonary fibrosis, arthritis, and cardiovascular diseases. Its involvement in these processes makes MMP7 a potential therapeutic target in various fibrotic and inflammatory conditions.

Therapeutic Target and Inhibitors

Given its significant role in disease progression, MMP7 has emerged as a potential target for therapeutic intervention. Several MMP inhibitors (MMPIs) have been developed, aiming to block the enzymatic activity of MMP7 and other MMPs. However, the clinical utility of these inhibitors has been limited by their lack of specificity and associated side effects. Ongoing research is focused on developing more selective MMP7 inhibitors with improved efficacy and safety profiles.

See Also

• Matrix metalloproteinase
• Extracellular matrix
• Cancer metastasis
• Enzyme inhibitor