The role of dietary fatty acids in the development and progression of cancer in human populations is controversial, but the effects on experimental cancer in animals is well documented. We have previously shown that linoleic and arachidonic acids, important dietary omega-6 polyunsaturated fatty acids, stimulate cell adhesion in human breast tumor cells, and promote invasion and peritoneal metastasis of human scirrhous gastric carcinoma cells. We are now investigating the mechanisms by which these fatty acids enhance tumor cell invasion. We have used differential display to identify the changes in gene expression between linoleic acid-treated and untreated OCUM-2MD3 cells. Plasminogen activator inhibitor 1 messenger RNA binding protein was identified as one of the differentially expressed genes; therefore, we investigated plasminogen activator inhibitor 1 (PAI-1) protein expression in cells and in media in linoleic acid-treated and -untreated cells. Linoleic acid induced PAI-1 expression in the media and enhanced cell invasion through Matrigel in a dose dependent manner. Furthermore, either inhibition of PAI-1 expression with RNA interference (RNAi) or blockage of PAI-1 activity with specific antibodies reduced the invasion ability of the OCUM-2MD3 cells. These data suggest that fatty acid-induced expression of PAI-1 is an important step in tumor cell invasion. Thus, inhibition of PAI-1 may be a novel approach for abrogating gastric cancer metastasis.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]