Gelatinase (MMP-2 and -9) expression in gastrointestinal malignancy

Abstract

Summary The aim of the study was to investigate expression of the active and inactive gelatinases (MMP-2 and -9) in colorectal neoplasia and gastric cancer compared with normal mucosa. A total of 53 colorectal cancers and corresponding normal mucosa were studied using gelatin zymography as well as 15 colorectal adenomas and 13 gastric cancers with corresponding normal mucosa. Overexpression of all the gelatinases occurs in both colorectal and gastric cancer, with activation of MMP-2 appearing to be a feature of the malignant phenotype. Overexpression of MMP-9 occurs in colorectal adenomas. The gelatinases are overexpressed in gastrointestinal neoplasia, suggesting that these enzymes may have an important role in tumour invasion and metastasis.

Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer

“…Thus there is not only more MMP-2 present in tumour than in normal tissue, but the ratio active to proenzyme also increases substantially. A similar finding was reported by Parsons et al (1998) and McKerrow et al (2000) and supports the view that the activation of MMP-2 is a crucial step in tumour invasion. Expression of MMP-2 mRNA in tumour has been described in stromal fibroblastic cells (Poulsom et al, 1992;Newell et al, 1994), but MMP-2 protein appears to be localised predominantly in the cytoplasm of tumour cells (Ring et al, 1997).…”

“…This finding is new since previous studies reported difficulty in measuring the active form, because of its unstability (Parsons et al, 1998) or presumed low levels (Liabakk et al, 1996). In CRC it has been shown that MMP-9 mRNA is expressed in macrophages especially in the invasive site.…”

“…It is suggested that MMP-9 levels reflect the presence of inflammatory infiltrate around the tumour rather than the characteristics of the tumour itself. However, Parsons et al (1998), did not find a correlation between MMP-9 and the amount of peritumoural lymphocytic infiltrates. Our observation that proMMP-9 increases more than its active form in tumour tissue may result from induced secretion of large amounts of proform by macrophages and neutrophils.…”

“…To some degree, all show enhanced gelatinase levels in tumour tissue, at least for the latent forms of MMP-2 and MMP-9. However, some studies (Liabakk et al, 1996;Parsons et al, 1998) have not quantified active MMP-9, while others (Garbett et al, 1999a;Zeng et al, 1999;Baker et al, 2000) do not report specific activities but rather the absence or presence of the various enzyme forms. A consistent quantification of both the latent and active forms -and their ratio -of both gelatinases in matched tumour and normal tissue is still lacking.…”

Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients

“…The gelatinases, MMP-2 and MMP-9, have been particularly implicated in tumour invasion and metastasis formation (Poulsom et al, 1992;Parsons et al, 1998;Zeng et al, 1999). The primary substrate for these enzymes is type IV collagen, a major component of the basement membrane, which represents a substantial barrier for tumour cell metastasis.…”