POLYAMINE-DEPENDENT EXPRESSION OF THE MATRIX METALLOPROTEINASE MATRILYSIN IN A HUMAN COLON CANCER-DERIVED CELL-LINE

Matrilysin, which is a member of the matrix metalloproteinase family a nd is implicated in colon cancer invasion, is expressed in human colon adenocarcinoma-derived SW1116 cells. We investigated the effect of al pha-difluoromethylornithine (DFMO) on matrilysin expression in this ce ll line because others have shown that DFMO can inhibit invasion and c arcinogenesis in epithelial tissues, including the colon, in experimen tal models. DFMO reduced extracellular levels of matrilysin protein af ter 4 d of treatment. Intracellular levels of matrilysin protein were minimally affected by DFMO treatment. The decrease in extracellular ma trilysin protein levels caused by DFMO was not a consequence of lowere d steady-state levels of matrilysin mRNA. After 4 d of exposure, the a mount of this transcript was higher in DFMO-treated cells than in untr eated cultures, whereas the mRNA stabilities were similar. These data show that polyamine depletion by DFMO can suppress the expression of m atrilysin, a gene product thought to be involved in tumor invasion. Th e decrease in extracellular matrilysin protein caused by DFMO treatmen t appears to be due to a posttranscriptional mechanism, although trans cription of this gene also seems to be affected by polyamines in SW111 6 cells. (C) 1994 Wiley-Liss, Inc.