Enhanced secretion and activation of matrilysin during malignant conversion of human colorectal epithelium and its relationship with invasive potential of colon cancer cells

Abstract

Matrilysin is a member of the matrix metalloproteinase gene family which is believed to play an important role in tumor progression. Matrilysin mRNA has been reported to be overexpressed in colorectal cancer. The aim of this study was to evaluate the enzyme activity of this protein during colorectal cancer. The aim of this study was to evaluate the enzyme activity of this protein during colorectal carcinogenesis and its relationship with the invasiveness of colorectal cancer cells. We have examined the levels of secreted matrilysin in various epithelial disorders of the colon using casein zymography. We have also examined the effect of matrilysin on the in vitro invasiveness of colorectal cancer cells using a modified Boyden Chamber method. The enzyme activities of matrilysin were detected in cancer tissue and adenoma tissue, whereas they were hardly detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis, and normal colon tissue. Enhanced secretion and enhanced activation of matrilysin were observed in cancer. An in vitro invasion assay revealed that the levels of secreted matrilysin-transfectants correlated positively with invasiveness. Our data suggest that the secretion and activation of matrilysin may be up-regulated during malignant conversion of colorectal epithelium. Matrilysin appears to contribute to in vitro invasiveness of colon cancer cells. Inhibitors of the enzyme may be of value in preventing colorectal cancer progression.