Influence of dietary linoleic acid an experimental human breast cancer cell metastasis in athymic nude mice

The effects of linoleic acid (LA), an omega-6 fatty acid precursor for pros taglandin biosynthesis, on the later stages of human breast cancer cell met astasis were studied by the intravenous injection of tumor cells into nude mice ('experimental metastasis'). MDA-MB-435 cells were grown as solid tumo rs in donor mice fed a 12% or 2% LA-containing diet. These cells were harve sted, and injected via a tail vein into recipient mice also fed a 12% LA (G roup 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 cul ture medium. At necropsy 8 weeks later, the incidence of metastatic lung no dules 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<0.0 5) compared with Groups 3 or 4. The extent of metastasis was significantly higher in Group 1 compared with any of the other groups, including metastas is to the ovaries, which occurred in 27% of the Group 1 mice. These finding s show that LA, most likely by increased synthesis of cyclooxygenase produc ts, stimulates metastasis, at least in part, by direct effects on the tumor cells, rather than on potential metastatic sites in the host.