Matrix metalloproteinases (MMPs), also known as matrixins, are so named because they require metal ions such as Ca and Zn as cofactors.
MMPs can degrade almost all kinds of protein components in the extracellular matrix ECM, destroy the histological barrier to tumor cell invasion, and play a key role in tumor invasion and transfer, thus their role in tumor infiltration and transfer has been increasingly emphasized, and they are considered to be the main protein hydrolases in this process.
Structural Features of the MMP Family
MMPs are a highly conserved class of enzymes comprising a family of zinc ion-dependent proteolytic enzymes that are widely distributed in plants, invertebrates, and vertebrates.
The MMP family has a common core structure. Typical MMPs consist of a prepeptide of about 80 amino acids, a metalloproteinase-catalyzed structural domain of 170 amino acids, a variable-length linker peptide or hinge region, and a heme protein structural domain of about 200 amino acids. Membrane-type MMPs (MT-MMPs) usually have transmembrane structural domains and cytoplasmic structural domains. MMP-17 and -25 have a glycosylphosphatidylinositol (GPI) anchor. MMP-23 can be in a potentially inactive form through its type II signaling anchor and has regions rich in cysteine and immunoglobulin-like proline.
MMP subtypes and structures
MMPs vary in size and act on different substrates, but have a high degree of structural homology. They roughly contain prepeptide structural domains, catalytic structural domains, signaling structural domains and heme-like structural domains. Based on the differences in structure and action substrates, MMPs can be broadly categorized into 5 groups:
| Type | Name | Action Substrate |
| Collagenase | MMP-1, 8, 13 | The substrates are mainly interstitial collagen, i.e., collagen types I, II, III, VII and X, and gelatin and collagen type IV cannot be degraded. |
| Gelatinase | MMP-2, 9 | Collagen type IV and gelatin, also degrades collagen types VII, IX, X, and laminin. |
| Stromelysin | MMP-3, 10, 11 | Proteoglycans and glycoproteins in the matrix, such as fibronectin and laminin. It can also degrade some collagen and activate some MMPs precursors. |
| Membrane type MMPs | MMP-14, 15, 16, 17, 24, 25 | Receptor and activator of MMPs, degrades collagen and laminin. |
| Other MMPs | MMP-19, 20, 23, 28 | ---- |
MMPs Cell Source and Cytologic Function
MMP is produced by a variety of tissues and cells. MMP is secreted by pro-inflammatory and uterine placental cells, including fibroblasts, osteoblasts, endothelial cells, vascular smooth muscle, macrophages, neutrophils, lymphocytes, and cytotrophoblasts. Dermal fibroblasts and leukocytes are the main sources of MMP, especially MMP-2. Platelets are an important source of MMP-1, MMP-2, MMP-3, and MMP-14.
They are present in most connective tissues. MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13 as well as MT1-MMP and MT3-MMP are expressed in various vascular tissues and cells.
MMPs are usually secreted as inactive proMMP, which is cleaved to its active form by various proteases including other MMPs. MMPs degrade various protein substrates in the ECM, including collagen and elastin. MMPs promote cell proliferation, migration, and differentiation and play a role in angiogenesis, apoptosis, and tissue repair. They affect endothelial cell function as well as migration, proliferation, Ca2+ signaling, and contraction of vascular smooth muscle cells. MMPs can also affect bioactive molecules on the cell surface and regulate various cellular and signaling pathways.
Relationship between MMPs and Cancer
Under normal physiological state, MMP and tissue inhibitors of metalloproteinases (TIMP) co-regulate the renewal of ECM and maintain cellular stability. MMP dysregulation can disrupt the tissue barrier to tumor invasion by promoting matrix degradation thereby facilitating tumor breakthroughs of the basement membrane and extracellular matrix, invasion into surrounding tissues, and metastasis to distant sites, or indirectly by releasing matrix-associated growth factors to promote tumor growth, invasion, and metastasis. The invasiveness of a tumor can be determined to a certain extent by detecting the expression level of MMPs around the tumor.
Therefore, MMPs have become attractive targets for tumor research and the development of antitumor drugs. Meanwhile, MMPs can regulate the adhesion of tumors to the stroma and influence the potency of adhesion factors.
Relationship between MMPs and Cancer
Jonlnbio MMPs ELISA Kits, to help researchers to study and explore the mechanism. The products are strictly quality-checked to ensure consistency between batches.
Hot Selling MMPs ELISA Kits
Selected Product Citation
Injectable postoperative enzyme-responsive hydrogels for reversing temozolomide resistance and reducing local recurrence after glioma operation.
IF=7.58
Journal: Biomaterials Science
DOI: 10.1039/D0BM00338G
Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model.
IF=5.60
Journal: Arthritis Research & Therapy
DOI: 10.1186/s13075-021-02684-8