SUPPRESSION OF TYPE-IV COLLAGENASE IN MDA-MB-435 HUMAN BREAST-CANCER CELLS BY EICOSAPENTAENOIC ACID IN-VITRO AND IN-VIVO

Dietary supplementation with 4% eicosapentaenoic acid (EPA), a long-ch ain polyunsaturated fatty acid, suppressed the development of lung met astases in nude mice from MDA-MB-435 human breast cancer cell mammary fat pad solid tumors. Zymography of primary tumor homogenates showed t hat this inhibition of metastasis was associated with reduced levels o f 92-kDa type IV collagenase gelatinolytic activity; this isoform has been previously associated with the metastatic phenotype. The 72-kDa i soform, which was also present, may have arisen from the cancer cells, or tumor-associated host cells. In vitro, the incorporation of EPA, 0 .25-1.0 mu g/ml into the medium caused a concentration-related suppres sion of cultured MDA-MB-435 cell 92-kDa type IV collagenase mRNA expre ssion.