Matrix Metalloproteinases

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are pivotal in the degradation of extracellular matrix (ECM) proteins. MMPs are widely involved in a variety of physiological and pathological processes, and plays an important role in cell migration, tissue remodeling, wound healing, and maintenance of ECM integrity, etc. Abnormal expression of MMPs can lead to tissue injury and disease deterioration. Consequently, MMPs have emerged as significant biomarkers and therapeutic targets in clinical diagnostics and treatment.

MMPs family structure characteristics

The matrix metalloproteinases represents a large family that requires metal ions as cofactors. Each MMP contains a conserved protease domain. Typically, MMPs are composed of a propeptide of about 80 amino acids, a catalytic metalloproteinase domain of about 170 amino acids, a linker peptide or hinge region of variable length, and a hemopexin domain of about 200 amino acids. MMPs are initially synthesized as inactive pro-MMPs, which undergo protein cleavage under physiological conditions to become active. This activation is facilitated by various proteases, including other MMPs^[1,2]。

Fig. 1. MMP subtypes and their structure^[1]

Different types of MMPs have distinct specific structural features. These specific structural features play a crucial role in their interactions with other molecules, thereby influencing or determining the activity, substrate specificity, cellular and tissue localization of MMPs. Based on the differences of the substrates and the homology of fragments, the MMP family can be classified into six categories: (1) Collagenases; (2) Gelatinases; (3) Hyaluronidases; (4) Matrix metalloproteinases; (5) Membrane-type MMPs; (6) Other MMPs.

Role in physiology and pathology

MMPs are a class of enzymes that have the function of remodeling extracellular matrix proteins. Under normal physiological conditions, MMPs are essential for various normal physiological processes such as embryonic development, morphogenesis, tissue remodeling, immune response, and defense mechanisms. MMPs can degrade almost all protein components in the extracellular matrix (ECM), destroy the histological barrier of tumor cell invasion, and play a key role in tumor invasion and metastasis. MMPs are considered to be an important proteolytic enzyme in this process. Notably, MMP-2 and MMP-9 are particularly significant in facilitating cancer metastasis and invasion. These MMP family proteases are key factors in extracellular matrix degradation and have become important targets for anticancer drug development. In addition, MMPs are also essential in the extravasation and tissue infiltration of white blood cells, and they play a key role in the development of inflammatory diseases.

Fig. 2. The role of MMPs in cancer disease^[3]