Table 1.
Contribution of MMPs to cancer progression and their main proteolytic activities. Individual MMPs are involved to varying degrees in different stages of cancer progression by activating other MMPs and cleaving ECM components as well as other pericellular molecules. Further MMP substrates that are not directly related to cell–matrix and cell–cell interaction can be found in the text.
| MMP | Involved In | Substrates | ||
|---|---|---|---|---|
| MMPs [47,57] |
ECM [15,47,57] |
Cell–Matrix and Cell–Cell Receptors [47,57] |
||
| MMP-1 | EMT [17,35], invasion and metastasis [36] |
proMMPs -1, -2, -9 |
collagens I, II, III, VII, VIII, X, XI, gelatin, elastin, fibronectin, vitronectin, aggrecan, neurocan, brevican, decorin, perlecan, laminin-5, nidogen, CTGF (CCN2), tenascin, SPARC, fibrinogen, fibrin, link protein | |
| MMP-2 | EMT [36] | proMMPs -1, -2, -9, -13, MMP-12 |
collagens I (a), III (a), IV (a), V (a), VII (a), X (a), XI (a), gelatin, elastin, fibrillin, fibronectin, vitronectin, aggrecan, laminin, nidogen, tenascin, fibrinogen, fibrin, decorin, link protein |
dystroglycan |
| MMP-3 | EMT [34,37], invasion and metastasis [36] |
proMMPs -1, -2, -3, -7, -8, -9, -13 | non-triple-helical regions of collagens III, IV, V, VII, IX, X, XI, collagen telopeptides, gelatin, elastin, fibrillin, fibronectin, vitronectin, aggrecan, versican, decorin, biglycan, perlecan, laminin, nidogen, fibulin, tenascin, SPARC, osteopontin, fibrinogen, fibrin, link protein, myelin basic protein |
E-cadherin [58] |
| MMP-7 | EMT [38], invasion and metastasis [36] |
proMMPs -1, -2, -7, -9 |
collagen IV (a), non-triple-helical regions of collagens IV, V, IX, X, XI, gelatin, elastin, fibronectin, vitronectin, aggrecan, brevican, versican, decorin, laminin, nidogen, fibulin, tenascin, SPARC, osteopontin, galectin-3, fibrinogen, fibrin, link protein, myelin basic protein |
E-cadherin [59], β4 integrin, syndecans -1, -2 [60] |
| MMP-8 | tumor angiogenesis [54] | proMMP-8 | collagens I, II, III, gelatin, aggrecan, link protein | |
| MMP-9 | EMT [36], invasion and metastasis [54], tumor angiogenesis [50] |
proMMPs -2, -9, -13, ADAMTS-4 (b) |
non-triple-helical regions of collagens I, IV, V, XI, XIV, collagens III (a), IV (a), V (a), gelatin, elastin, fibrillin, fibronectin, vitronectin, aggrecan, versican, decorin, biglycan, laminin, nidogen, SPARC, galectins -1 and -3, fibrinogen, fibrin, link protein, myelin basic protein |
E-cadherin, β2 integrin, dystroglycan |
| MMP-10 | invasion and metastasis [51], tumor angiogenesis [51] | proMMPs -1, -2, -7, -8, -9, -10, -13 |
collagens I (a), III (a), IV (a), V (a), gelatin, elastin, fibronectin, aggrecan, brevican, laminin-5, link protein, fibrinogen | |
| MMP-11 | invasion and metastasis [51] | proMMPs -2, -11 |
collagen IV (a), gelatin, fibronectin, aggrecan, laminin | |
| MMP-12 | collagens (a) I, IV, V, gelatin, elastin fibrillin, fibronectin, vitronectin, aggrecan, decorin, biglycan, laminin, nidogen, SPARC, fibrinogen, fibrin, myelin basic protein |
|||
| MMP-13 | invasion and metastasis [36] | proMMPs -2, -9, -13 |
collagens I, II, III, VI, VII, IX, X, XIV, gelatin, fibrillin, fibronectin, aggrecan, brevican core protein precursor, biglycan, perlecan, laminin-γ2, nidogen, CTGF (CCN2), tenascin, large tenascin C, SPARC, fibrinogen |
|
| MMP-14 | EMT [39,40], invasion and metastasis [36], tumor angiogenesis [17,55] |
proMMPs -2, -8 [61], -13, -14, MMP-14, ADAM9 (b) |
collagens I, II, III, gelatin, tropoelastin [62], elastin [62], fibrillin, fibronectin, vitronectin, aggrecan, perlecan, lumican, nidogen, laminins -1, -2, -4, -5, CTGF, CTGF-L (CCN5), Cyr61 (CCN1), tenascin, galectins -1 and -3, fibrinogen, fibrin, myelin basic protein |
E-cadherin, N-cadherin, ICAM-1, αV integrin, syndecan-1, syndecan-2 [60], CD44, ICAM-1, DLL1, EMMPRIN |
| MMP-15 | proMMPs -2, -13 |
collagen (a) I, NC1 (collagen IV), fibronectin, aggrecan, perlecan, laminin-1, nidogen, tenascin, fibrinogen, fibrin, myelin basic protein |
||
| MMP-16 | invasion and metastasis [36] | proMMP-2 | collagen III (a), gelatin, fibronectin, vitronectin, laminin-1, fibrin, myelin basic protein |
|
| MMP-17 | proMMP-2, ADAMTS4 (b) |
gelatin, fibronectin, laminin-1, chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, fibrinogen, fibrin, myelin basic protein |
N-cadherin | |
| MMP-19 | proMMP-19, MMP-9 |
collagen IV (a), gelatin, fibronectin, aggrecan, laminin, nidogen-1, tenascin, large tenascin-C, COMP, fibrinogen, fibrin |
||
| MMP-20 | proMMP-20 (autolysis) |
collagen XVIII (a), gelatin, aggrecan, laminin, COMP, amelogenin, ameloblastin | ||
| MMP-21 | gelatin, aggrecan | |||
| MMP-23 | gelatin, fibronectin | |||
| MMP-24 | proMMP-2, ADAMTS4 (b) |
gelatin, fibronectin, chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, fibrinogen, fibrin |
||
| MMP-25 | proMMPs -2, -9 |
collagen IV (a), gelatin, fibronectin, laminin-1, chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, SPARC, galectin-1, fibrinogen, fibrin, myelin basic protein |
||
| MMP-26 | invasion and metastasis [36] | proMMPs -9, -26 |
collagen IV (a), gelatin, fibronectin, vitronectin, fibrinogen | |
| MMP-27 | proMMP-27 (autolysis) |
gelatin | ||
| MMP-28 | EMT [41], invasion and metastasis [36] |
NCAM | ||
(a) While MMPs -1, -8, -13, and -14 are true collagenases that can cleave triple-helical collagens, other MMPs can only cleave single collagen chains after unwinding of their triple helix. (b) Although this is not an MMP, it is listed here because of its related activity.