EXPRESSION AND LOCALIZATION OF MATRIX-DEGRADING METALLOPROTEINASES DURING COLORECTAL TUMORIGENESIS

The metalloproteinase matrilysin is widely expressed in the epithelial tumor cells of malignant colorectal adenocarcinomas. Approximately 50 % of benign adenomas also express low levels of matrilysin that is foc ally localized. The expression of stromelysin-1, stromelysin-3, and ge latinase A was observed in the stromal component of several carcinomas and was not present in adenomatous tissue. The expression of intersti tial collagenase and gelatinase B was observed in occasional adenomas and carcinomas Stromelysin-2 transcripts were not detectable in any of the samples examined. Tissue inhibitor of metalloproteinase-l gene ex pression was widespread and was observed in both epithelial and stroma l cells of adenomas and carcinomas. These results indicate that matril ysin gene expression is an early event in colorectal tumorigenesis and that the expression of stromelysin-l, stromelysin-3, and gelatinase A is primarily a late event. The observed gene expression patterns sugg est that matrilysin may participate in early events in tumor progressi on and that multiple members of the metalloproteinase family may work in concert to facilitate late-stage tumor invasion and metastasis. (C) 1994 Wiley-Liss, Inc.