Dietary omega-3 polyunsaturated fatty acids promote colon carcinoma metastasis in rat liver.
The effects of omega-3 polyunsaturated fatty acids (PUFAs) and omega-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 (omega-3 PUFAs) or safflower oil (omega-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, omega-3 and omega-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.
Griffini
P
P
Academic Medical Center, University of Amsterdam, Department of Cell Biology and Histology, The Netherlands.
Fehres
O
O
Klieverik
L
L
Vogels
I M
IM
Tigchelaar
W
W
Smorenburg
S M
SM
Van Noorden
C J
CJ
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002455:Cell Division / Q000502:physiology; D003110:Colonic Neoplasms / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000633:toxicity*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000633:toxicity; D005260:Female; D007694:Killer Cells, Natural / Q000276:immunology; D007728:Kupffer Cells / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000209:etiology* / Q000276:immunology / Q000556:secondary*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated