Table 2.
Overview of MMPs with known roles in the development of colitis and/or CAC.
| MMP | Alternate names | Substrates | Role | Involvement in CAC | Refs |
|---|---|---|---|---|---|
| MMP-1 | Collagenase-1 | Types I-III collagen | Cell migration, reepithelization, TNF activation | Upregulated in UC and CD; involvement in CAC unknown | (89) |
| MMP-2 | Type IV collagenase, gelatinase A | Collagen, gelatin | Neurite outgrowth, cell migration | Assists in epithelial barrier maintenance to prevent initiation of colitis | (22, 89) |
| MMP-3 | Proteoglycanase, stromelysin-1 | Proteoglycan, casein, fibronectin, laminin | Adipocyte proliferation, antithrombotic activity, wound healing | Upregulated in UC | (90–92) |
| MMP-7 | Matrilysin-1 | Gelatin, laminin, fibronectin, vitronectin, and elastin | CRC metastasis, adipocyte differentiation | Upregulated in IBD-associated dysplasia | (89, 93–96) |
| MMP-8 | Collagenase-2 | Fibrils of types I- III collagen | Involved in neutrophilic infiltration | Upregulated in UC | (97, 98) |
| MMP-9 | Gelatinase B | Gelatin, collagen, elastin | Trophoblastic invasion, neo-vascularization, macrophage and neutrophil activation | Mediates inflammation in colitis; attenuates tumorigenesis in CAC | (99–102) |
| MMP-10 | Stromelysin-2 | Proteoglycan, casein, fibronectin, laminin | Wound healing | Resolution of inflammation; MMP-10 deletion increases murine CAC burden | (103, 104) |
| MMP-11 | Stromelysin-3 | Serpins, e.g., a2-macroglobulin, a1-proteinase inhibitors | Adipocyte de-differentiation, desmoplastic reaction in cancer-adjacent tissue, early tumor invasion | Attenuated CRC cell apoptosis in MMP-11-deficient mice; expression reduced by infliximab treatment in a murine IBD model, suggesting a contributory role in CAC | (105–108) |
| MMP-13 | Collagenase-3 | Fibrils of type I-III collagen | Osteoclast and TNF activation | Associated with increased intestinal permeability upon inflammation, and upregulated in colitis | (89, 109) |
| MMP-14 | MT1-MMP | Collagen type I-III, gelatin, CD44, pro-MMP-2, -8, and -13 | Cell migration, cytotrophoblast invasion | Upregulated in cancer-associated fibroblasts found in CAC | (65, 96) |
TNF, tumor necrosis factor; UC, ulcerative colitis; CD, Crohn’s disease; CAC, colitis-associated cancer; IBD, inflammatory bowel disease; Refs, references.