The effects of linoleic acid (LA), an omega-6 fatty acid precursor for prostaglandin biosynthesis, on the later stages of human breast cancer cell metastasis were studied by the intravenous injection of tumor cells into nude mice (). MDA-MB-435 cells were grown as solid tumors in donor mice fed a 12% or 2% LA-containing diet. These cells were harvested, and injected via a tail vein into recipient mice also fed a 12% LA (Group 1) or 2% LA (Group 2) diet. Other groups were fed 12% LA (Group 3) or 2% LA (Group 4), but injected with the cells grown in vitro in a low-LA culture medium. At necropsy 8 weeks later, the incidence of metastatic lung nodules was higher in Group 1 high LA donor/high LA recipient mice (p<0.001), and, to a lesser degree, Group 2 low LA donor/low LA recipient mice (p<0.05) compared with Groups 3 or 4. The extent of metastasis was significantly higher in Group 1 compared with any of the other groups, including metastasis to the ovaries, which occurred in 27% of the Group 1 mice. These findings show that LA, most likely by increased synthesis of cyclooxygenase products, stimulates metastasis, at least in part, by direct effects on the tumor cells, rather than on potential metastatic sites in the host.
