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.
Academic Medical Center, University of Amsterdam, Department of Cell Biology and Histology, The Netherlands.
P
P
Griffini
O
O
Fehres
L
L
Klieverik
I M
IM
Vogels
W
W
Tigchelaar
S M
SM
Smorenburg
C J
CJ
Van Noorden
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