Eicosanoids and linoleate-enhanced growth of mouse mammary tumor cells

Metastatic mouse mammary tumor cell line 4526 was used to determine whether linoleate (LN)-derived cyclooxygenase metabolites were involved in the mechanism of LN-enhanced 4526 tumor growth. Unstimulated line 4526 cells converted LN to both PGE1 and PGE2 in serum free medium (SFM). However, neither prostaglandin (PG) influenced growth, while db-cGMP, but not db-cAMP, stimulated growth to the same extent as LN. Cyclooxygenase inhibitors stimulated growth while suppressing PG synthesis. Lipoxygenase inhibitors decreased growth in a dose dependent manner. Supplemental LN had no effect on cyclooxygenase inhibition while the IC50s for lipoxygenase inhibition were increased several fold. These results indicate that lipoxygenase products rather than cyclooxygenase metabolites play a major role in LN-stimulated growth of line 4526 cells.