Matrix metalloproteinases (MMPs) constitute a family of structurally related zinc-dependent endopeptidases capable of degrading basement membrane and all components of the extracellular matrix. Tissue inhibitors of metalloproteinases (TIMPs) inhibit the proteolytic activity of MMPs. The balance between metalloproteinases and their inhibitors has been shown to be important in the development of pancreatic cancer. Pancreatic cancer progression is associated with changes in the levels of MMP and TIMP expression. The overexpression of MMP-7 is significantly associated with metastasis and the 1-year survival rate in pancreatic cancer. MMPs perform multiple roles including tissue remodeling, repair, and modulation of immune responses. In healthy tissues, MMPs are rarely expressed: their biological activity is tightly regulated by various mechanisms. Excessive MMP production has been reported in diverse inflammatory conditions such as cancer, chronic obstructive pulmonary disease, sarcoidosis, interstitial lung disease, arthritis, and atherosclerosis. MMP-7 is produced mainly by glandular epithelial cells and macrophages in diseased tissues and is overexpressed by cancer cells in human tumors. It has been linked to the development of metastases and is also considered to play a role in tumorigenesis and tumor progression. MMP-7 (matrilysin) cleaves collagen IV, elastin, intactin, fibronectin, gelatin, laminin and tenascin, and is known to be involved in several lung malignancies and non-malignancies, including IPF and NSCLC. MMP-7 has been found to be over-expressed in several tumors, such as those associated with esophageal, cholangiocarcinoma, gastric, colon, prostate and bladder cancer. Huang et al (2005) have reported that MMP-7 is a major matrix metalloproteinase associated with tissue remodeling during the progression of liver fibrosis in biliary atresia. Zuo et al (2002) have identified expression of MMP-7 as a mediator of pulmonary fibrosis and reported that knock-out mice lacking expression of MMP-7 are protected from pulmonary fibrosis in response to intratracheal bleomycin. Saarialho-Kere et al (1996) have reported enhanced expression of MMP-7 in gastrointestinal ulcers, suggesting a significant role in epithelial remodelling occurring in gastrointestinal ulcerations. Matsuno et al (2003) have reported that MMP-7 appears to be expressed only in the epithelial cells on the edge of ulcers and indicates the degree of inflammation in ulcerative colitis. Clinical use and areas of investigation: - Pancreatic cancer - Colorectal cancer - Inflammatory diseases - Tissue regeneration
- References to MMP-7 (Matrix metalloproteinase-7)