STIMULATION OF TYPE-IV COLLAGENASE EXPRESSION BY LINOLEIC-ACID IN A METASTATIC HUMAN BREAST-CANCER CELL-LINE

Linoleic acid (LA), an omega-6 fatty acid, enhanced the appearance of type IV collagenase activity in culture medium conditioned by the metastatic MDA-MB-435 human breast cancer cell line; this effect was maximal with 0.75 mu g/ml LA. Zymography showed an increase in the gelatinolytic 92 kDa metalloproteinase, a form associated with the metastatic phenotype, during culture in the presence of 0.75 mu g/ml LA. Indomethacin, 20 mu g/ml, completely suppressed the stimulation of collagenase by LA, suggesting a role for the eicosanoids. The tumor cells expressed mRNA for both the 72 and 92 kDa isoforms of type IV collagenase. Basal levels of the 92 kDa mRNA were much higher; both were up-regulated by LA despite the absence of detectable 72 kDa activity in conditioned medium.