Synthesis of Specific Lipids Associated with the Hormone-Induced Resistance of Tumor Cells to Humoral Immune Killing

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Abstract
Selected polypeptide (insulin), catecholamine (epinephrine), and glucocorticosteroid hormones (hydrocortisone and prednisolone) that increase the resistance of line-1 guinea pig hepatoma cells to humoral immune killing were studied for their effects on the ability of the cells to synthesize lipids. Line-1 tumor cells incubated for 1 hr at 37°C with 10-7 to 10-9 M concentrations of any of these hormones became more resistant to killing by antibody plus GPC and exhibited increased levels of fatty acid incorporation into lipids compared to untreated cells. Cells incubated with hormone for 4 hr at 37°C became as susceptible to antibody-GPC killing as untreated cells; lipid synthesis in these cells likewise reverted to control levels. When the reverted cells were reincubated with a different, but not the same, hormone, they were again rendered more resistant to antibody-GPC killing and their lipid synthesis was restimulated. Thin layer chromatography of lipid extracts from hormone-treated as well as from restimulated cells indicated that the increased resistance of the cells to killing correlated with increased synthesis of phosphatidyl choline, phosphatidyl serine, and, in some instances, triglycerides. The cells' reversion to the susceptible state during prolonged incubation with hormone or restimulation with the same hormone was accompanied by a reduction in the synthesis of these lipids along with an increase in cholesteryl ester and cardiolipin synthesis. The synthesis of specific phospholipids and neutral lipids, therefore, rather than lipid synthesis in general, appears to be associated with the mechanism whereby these tumor cells resist humoral immune killing.