Matrix Metalloproteinase Expression in Lung Cancer
The importance of matrix metalloproteinases (MMPs) in the growth and spread of solid tumors has been known for over a decade (1 ,2) . However, the molecular mechanisms that regulate their expression and the elucidation of their role in angiogenesis are subjects of extensive, ongoing investigation. The MMPs are a family of extracellular, zinc-dependent proteinases that control tumor growth via tumor promotion (3) and angiogenesis (2 ,4) . They are secreted as latent proenzymes and become activated after cleavage of their propeptide domain. MMPs are regulated on several levels including transcription, protein activation, and the interaction with endogenous inhibitors such as the tissue inhibitors of metalloproteinases (TIMPs) (5) . Over 20 MMPs have been described to date (6 ; see Table 1) . Although traditionally subclassified according to substrate specifi city (e.g., collagenases, gelatinases, stromelysins), collectively they are capable of breaking down all of the components of the extracellular matrix (ECM), including components of basement membranes (BMs) and submucosa (1 ,5 ,6) . MMP-2 and MMP-9, gelatinase A and B, respectively, are of particular interest because they degrade type IV collagen, the major component of basement membranes. Recently, Fang et al. (7) demonstrated in an animal model of chondrosarcoma that MMP-2 shifts the “proteolytic balance” towards an angiogenic phenotype, and is required for new blood vessel formation.
Table 1 Matrix Metalloproteinase Classifi cation | ||
MMP family | MMP number | Common name |
Collagenases | 11 | Interstitial collagenase |
18 | Neutrophil collagenase | |
13 | Collagenase-3 | |
18 | Xenopus collagenase | |
Gelatinases | 12 | Gelatinase A |
19 | Gelatinase B | |
Stromelysins | 13 | Stromelysin-1 |
10 | Stromelysin-2 | |
11 | Stromelysin-3 | |
17 | Matrilysin | |
Elastase | 12 | Metalloelastase |
Membrane-type | 14 | MT-MMP-1 |
15 | MT-MMP-2 | |
16 | MT-MMP-3 | |
17 | MT-MMP-4 | |
21 | MT-MMP-5 | |
Unclassifi ed | 20 | Enamelysin |
19 | ||
23 | ||
24 | ||
Adapted from ref. 6 . |
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