Matrix metalloproteinases (MMPs) are zinc-dependent and calcium-dependent proteases that degrade most components of the extracellular matrix (ECM) and process a number of bioactive molecules. Collagenases are MMPs that share the ability to cleave the native helix of fibrillar collagens at a single peptide bond. Collagenase-1 (MMP1 or interstitial collagenase) and collagenase-2 (MMP8 or neutrophil collagenase) initiate the breakdown of the extracellular matrix by degrading native interstitial collagen types I, II, and III. They cleave the helical collagen molecule at a single Gly-Ile/Leu bond in each alpha-chain of the molecule. The cleavage generates fragments that spontaneously lose their helical conformation, denature to gelatin, and become soluble. The gelatin is then susceptible to attack by gelatinases and other proteases [].Neutrophil collagenase (MMP8) may play a role in the degradation of collagen fibres during postpartum uterine involution [].
Matrix metalloproteinases (MMPs) are zinc-dependent and calcium-dependent proteases that cleave within a polypeptide (endopeptidases). They degrade most components of the extracellular matrix (such as growth factors, their binding proteins, and other bioactive molecules, as well as binding sites for cell-surface molecules) and some non-extracellular-matrix molecules []. Two categories of MMPs can be recognised based on their cellular localisation: soluble vs. membrane-bound. The soluble MMPs are divided into the collagenases (MMP1, MMP8 and MMP13), gelatinases (MMP2 and MMP9), stromelysins (MMP3, MMP12) and those yet to be classified. The membrane-bound MMPs include MT1, 2, 3, 4, 5 and their hallmark is the presence of plasma membrane anchoring domains []. MMPs are highly expressed in various cancers, both by tumour cells and in surrounding stromal cells such as macrophages []. Matrix metalloproteinase-15 (MMP15; MEROPS identifier M10.015) or membrane-type matrix metalloproteinase 2 degrades various components of the extracellular matrix [, ]. The increase expression of MMP15 has been linked to cancer progression [].
Matrix metalloproteinases (MMPs) are zinc-dependent and calcium-dependent proteases that cleave within a polypeptide (endopeptidases). They degrade most components of the extracellular matrix (such as growth factors, their binding proteins, and other bioactive molecules, as well as binding sites for cell-surface molecules) and some non-extracellular-matrix molecules []. Two categories of MMPs can be recognised based on their cellular localisation: soluble vs. membrane-bound. The soluble MMPs are divided into the collagenases (MMP1, MMP8 and MMP13), gelatinases (MMP2 and MMP9), stromelysins (MMP3, MMP12) and those yet to be classified. The membrane-bound MMPs include MT1, 2, 3, 4, 5 and their hallmark is the presence of plasma membrane anchoring domains []. MMPs are highly expressed in various cancers, both by tumour cells and in surrounding stromal cells such as macrophages []. Matrix metalloproteinase-24 (MMP24; MEROPS identifier M10.023), or membrane-type matrix metalloproteinase 5 (MT5), activates progelatinase A (also known as MMP-2), which is involved in diverse functions such as remodelling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture []. MMP24 may play an important role in extracellular matrix remodelling events in the brain and during embryonic development [].
Matrix metalloproteinases (MMPs) are zinc-dependent and calcium-dependent proteases that cleave within a polypeptide (endopeptidases). They degrade most components of the extracellular matrix (such as growth factors, their binding proteins, and other bioactive molecules, as well as binding sites for cell-surface molecules) and some non-extracellular-matrix molecules []. Two categories of MMPs can be recognised based on their cellular localisation: soluble vs. membrane-bound. The soluble MMPs are divided into the collagenases (MMP1, MMP8 and MMP13), gelatinases (MMP2 and MMP9), stromelysins (MMP3, MMP12) and those yet to be classified. The membrane-bound MMPs include MT1, 2, 3, 4, 5 and their hallmark is the presence of plasma membrane anchoring domains []. MMPs are highly expressed in various cancers, both by tumour cells and in surrounding stromal cells such as macrophages []. Matrix metalloproteinase-17 (MMP17; MEROPS identifier M10.017) or membrane-type matrix metalloproteinase 4 degrades various components of the extracellular matrix, such as fibrin. It may be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators, such as tumour necrosis factor-alpha []. It may also be involved in tumour progression [, ].
Matrix metalloproteinases (MMPs) are zinc-dependent and calcium-dependent proteases that cleave within a polypeptide (endopeptidases). They degrade most components of the extracellular matrix (such as growth factors, their binding proteins, and other bioactive molecules, as well as binding sites for cell-surface molecules) and some non-extracellular-matrix molecules []. Two categories of MMPs can be recognised based on their cellular localisation: soluble vs. membrane-bound. The soluble MMPs are divided into the collagenases (MMP1, MMP8 and MMP13), gelatinases (MMP2 and MMP9), stromelysins (MMP3, MMP12) and those yet to be classified. The membrane-bound MMPs include MT1, 2, 3, 4, 5 and their hallmark is the presence of plasma membrane anchoring domains []. MMPs are highly expressed in various cancers, both by tumour cells and in surrounding stromal cells such as macrophages []. 72kDa type IV collagenase, also known as 72kDa gelatinase or matrix metalloproteinase-2 (MMP2; MEROPS identifier M10.003), is a ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumour invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction [, ]. PEX, a naturally occurring fragment of human MMP2, acts as an inhibitor of cell proliferation, migration, and angiogenesis [, ].
Matrix metalloproteinases (MMPs) are zinc-dependent and calcium-dependent proteases that cleave within a polypeptide (endopeptidases). They degrade most components of the extracellular matrix (such as growth factors, their binding proteins, and other bioactive molecules, as well as binding sites for cell-surface molecules) and some non-extracellular-matrix molecules []. Two categories of MMPs can be recognised based on their cellular localisation: soluble vs. membrane-bound. The soluble MMPs are divided into the collagenases (MMP1, MMP8 and MMP13), gelatinases (MMP2 and MMP9), stromelysins (MMP3, MMP12) and those yet to be classified. The membrane-bound MMPs include MT1, 2, 3, 4, 5 and their hallmark is the presence of plasma membrane anchoring domains []. MMPs are highly expressed in various cancers, both by tumour cells and in surrounding stromal cells such as macrophages []. Matrix metalloproteinase-16 (MMP16; MEROPS identifier M10.016), also called MT3-MMP, degrades various components of the extracellular matrix, such as collagen type III and fibronectin. It has no effect on type I, II, IV and V collagen. However, upon interaction with CSPG4, it may be involved in degradation and invasion of type I collagen by melanoma cells []. MMP-16 can not only directly degrade some matrix molecules, but can also activate pro-MMP-2 (gelatinase A), one of the most important MMPs in tissue remodelling and cell migration [, ].
Matrix metalloproteinases (MMPs) are zinc-dependent and calcium-dependent proteases that cleave within a polypeptide (endopeptidases). They degrade most components of the extracellular matrix (such as growth factors, their binding proteins, and other bioactive molecules, as well as binding sites for cell-surface molecules) and some non-extracellular-matrix molecules []. Two categories of MMPs can be recognised based on their cellular localisation: soluble vs. membrane-bound. The soluble MMPs are divided into the collagenases (MMP1, MMP8 and MMP13), gelatinases (MMP2 and MMP9), stromelysins (MMP3, MMP12) and those yet to be classified. The membrane-bound MMPs include MT1, 2, 3, 4, 5 and their hallmark is the presence of plasma membrane anchoring domains []. MMPs are highly expressed in various cancers, both by tumour cells and in surrounding stromal cells such as macrophages []. This entry represents matrix metalloproteinase-9 (MMP9, also known as gelatinase B), which is involved in matrix remodelling during the normal processes of embryogenesis, tissue remodelling and development []. It is released extracellularly in a pro-form with the enzymatic site covered by a propeptide that has to be cleaved off to reveal the activity. MMP9 can cleave gelatin types I and V and collagen types IV and V []. It plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration [, ]. MMP9 is one of the key regulators for remodelling skeletal tissues [], and could play a role in bone osteoclastic resorption triggered by inflammatory processes [, ]. MMP9 also has a role in synaptic plasticity []. MMP9 cleaves the metastasis suppressor gene product KiSS1 [].
