NEOPLASTIC PROGRESSION OF HUMAN COLORECTAL-CANCER IS ASSOCIATED WITH OVEREXPRESSION OF THE STROMELYSIN-3 AND BM-40 SPARC GENES/

The interaction of neoplastic cells with the extracellular matrix is a critical event for the initiation of cancer invasion and metastasis. This study was designed to evaluate the potential implication of strom elysin-3 (ST3), a newly identified member of the matrix-degrading meta lloproteinase family, and of BM-40/ SPARC, a glycoprotein associated w ith the extracellular matrix, during the progression of human colorect al cancers. We analyzed the relative abundance of ST3 and BM-40/SPARC transcripts by Northern blot, and their distribution by in site hybrid ization, in normal mucosa, benign adenomas, and primary colorectal ade nocarcinomas and their liver metastases. The ST3 and BM-40/SPARC trans cripts were overexpressed in primary colorectal cancers and their live r metastases compared to non-neoplastic mucosa. These transcripts were localized in stromal fibroblasts adjacent to the neoplastic foci. Ove rexpression of ST3 correlated with the progression of human colorectal tumors toward local invasion and liver metastasis. Induction of these genes also occurred in diverticulitis and digestive neoplasms such as gastric and esophageal carcinomas. (C) 1995 Wiley-Liss, Inc.