Matrilysin (matrix metalloproteinase‐7) expression in ulcerative colitis–related tumorigenesis†

Abstract

Matrilysin (matrix metalloproteinase-7) plays a part in the initiation and growth of colorectal tumors; expression of this protein has been implicated in tumor invasion and metastasis. To date, matrilysin expression in ulcerative colitis (UC)-associated tumorigenesis has not been studied. The aim of this study was to assess the immunohistochemical expression of matrilysin at different stages of UC-associated neoplasia. Paraffin-embedded specimens from 25 patients with UC without dysplasia, UC-related low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and UC-associated carcinoma as well as four colon biopsy samples with no abnormality were examined using an anti-human matrilysin monoclonal antibody and standard immunoperoxidase techniques. Matrilysin expression was recorded as the number of positive cases and the percentage of positive crypts as follows: normal: none of four; negative results for dysplasia: seven of 12 (< 10%); LGD: nine of 15 (< 10%); HGD: nine of 13 (11-50%); and invasive carcinoma: six of seven (> 50%). The results indicated an apparent switch from focal expression of matrilysin in UC-related low-grade dysplasia to widespread expression in high-grade dysplasia and invasive cancer, mimicking the pattern of expression in sporadic colorectal cancer. Although the sample size is small and further investigation therefore is required, the results suggest the possible role of anti-matrix metalloproteinase therapy in reducing the risk of progression from LGD to cancer in patients with ulcerative colitis. Published 2002 Wiley-Liss, Inc.

Stimulation of MMP-7 (matrilysin) byHelicobacter pyloriin human gastric epithelial cells: role in epithelial cell migration

“…However, this function seems to be species specific since, in human small intestine, trypsin has been reported to function as a prodefensin-processing enzyme (Ghosh et al, 2002). Moreover, in normal human small and large intestine, MMP-7 was reported to be absent (Ghosh et al, 2002), although expression may increase in ulcerative colitis in association with dysplasia (Newell et al, 2002). By contrast, we found detectable expression of MMP-7 in epithelial cells in both antral and corpus regions of normal human stomach, and in both cases expression was increased in the presence of the gastric pathogen H. pylori.…”

Matrix metalloproteinase-7-catalyzed release of HB-EGF mediates deoxycholyltaurine-induced proliferation of a human colon cancer cell line

“…Previous reports indicate that MMP-7 (also known as matrilysin; EC 3.4.24.23) catalyzes release of HB-EGF [36]. Moreover, in clinical studies, expression of MMP-7 increases progressively with more advanced grades of colonic epithelial dysplasia and cancer [38][39][40] and, in a rodent model, the formation of intestinal tumors is reduced in Min mice that do not express MMP-7 [41]. Hence, experimental data support a role for MMP-7 in facilitating colon carcinogenesis.…”

Insulin-Like Growth Factor Binding Protein-5 Is a Target of Matrix Metalloproteinase-7: Implications for Epithelial-Mesenchymal Signaling

“…Most MMPs are produced in subepithelial cells, but an exception is MMP-7 (matrilysin or PUMP) that is predominantly expressed in epithelial cells including those of the gastrointestinal tract, airways, mammary gland, and urogenital tract (7)(8)(9). There is increased MMP-7 expression in many tumors, in bacterial infections of normal epithelia, in inflammation, and in injury (9)(10)(11)(12)(13). In addition to digestion of extracellular matrix proteins, it is now clear that MMP-7 like other MMPs, may act on a variety of substrates to liberate growth factors and other signaling molecules, thereby potentially producing a diverse range of cellular responses (3,8,12,14,15).…”