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Dietary -3 Polyunsaturated Fatty Acids Promote Colon Carcinoma Metastasis in Rat Liver¹

Academic Medical Center, University of Amsterdam, Department of Cell Biology and Histology, 1100 DE Amsterdam, the Netherlands

The effects of -3 polyunsaturated fatty acids (PUFAs) and -6 PUFAs on the development of experimentally induced colon carcinoma metastasis in rat liver were investigated quantitatively in vivo. Rats were kept on either a low-fat diet or on a fish oil (-3 PUFAs) or safflower oil (-6 PUFAs) diet for 3 weeks before the administration of colon cancer cells to the portal vein, until they were sacrificed at 1 or 3 weeks after tumor transplantation. At 1 week after transplantation, the fish oil diet had induced 7-fold more metastases (in terms of number and size) than had the low-fat diet, whereas the safflower oil diet had not affected the number and total volume of metastases. At 3 weeks after tumor transplantation, the fish oil diet and the safflower oil diet had induced, respectively, 10- and 4-fold more metastases (number) and over 1000- and 500-fold more metastases (size) than were found in the livers of rats on the low-fat diet. These differences were sex independent. Immunohistochemical analysis revealed that the immune system in the liver (Kupffer cells, pit cells, T cells, newly recruited macrophages, and the activation state of macrophages) did not play a significant role in this diet-dependent outgrowth of tumors. In conclusion, -3 and -6 PUFAs promote colon cancer metastasis in the liver without down-regulating the immune system. This finding has serious implications for the treatment of cancer patients with fish oil diet to fight cachexia.

¹ This study was performed in the Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam as part of the postdoctoral research project of P. G. on a bursary of the Netherlands Orgnaization for International Cooperation in Higher Education (NUFFIC) bursary.

² O. F. and L. K. contributed equally to this work.

³ To whom requests for reprints should be addressed, at Academic Medical Center, University of Amsterdam, Department of Cell Biology and Histology, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands. Phone: 31-0-20-5664970; Fax: 31-0-20-6974156; E-mail: c.j.vannoorden@amc.uva.nl.

Received 4/22/98. Accepted 6/16/98.

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