Changes in Tumor Membrane Structure and Immunologic Activity Induced by Dietary Omega-3 Fatty Acids
Omega-3 fatty acids, abundant in fish oil, are associated with health benefits for diseases including cancer. We are exploring how the incorporation of dietary docosahexaenoic acid (DHA, 22:6 ῶ-3), the most unsaturated fatty acid found in biological systems, into tumor cell plasma membranes alters the tumor cell’s susceptibility to immune attack. Mice were fed diets containing 10.5% fat in various combinations of corn oil, hydrogenated coconut oil, and menhaden (fish) oil, and were inoculated intraperitoneally with a murine leukemia. The tumors that grew were tested for susceptibility to T-cell-mediated lysis and lysis with monoclonal anti-H-2 antibody plus complement, expression of H-2 proteins by radioimmunoassay, and changes in membrane structure. The tumor plasma membranes were analysed for phospholipid class and fatty acid content. Tumor cell sensitivity to cell-mediated lysis correlated positively with DHA content in tumor membranes. In contrast, complement-mediated cytolysis directed by a monoclonal antibody against an epitope on Dd was reduced as a function of dietary fish oil, suggesting, as did radioimmunoassay, a DHA-associated decrease in this epitope’s expression. The expression of other epitopes, however, was increased or unchanged. DHA-rich membranes showed an increased proportion of liquid crystalline domains, but little change in global fluidity. Although a benefit of fish oil diets has not been linked through epidemiological evidence to this type of cancer, our results showed decreased morbidity and reduced tumor growth when the tumor-bearing hosts were fed diets rich in fish oil. We propose that the structural changes in tumor cell membranes induced by dietary DHA alter the expression of membrane proteins targeted by the immune system, and thus may in part be responsible for decreased tumor growth.