Identification of lipids associated with the ability of tumor cells to resist humoral immune attack.
Certain metabolic inhibitors or chemotherapeutic agents that increase the susceptibility of line-1 or line-10 guinea pig hepatoma cells to humoral immune attack were studied for their effects on the ability of the cells to synthesize lipids. A direct correlation was found between the drug-induced increase in sensitivity to antibody-C mediated killing and the inhibition of the ability of the cells to incorporate acetate, glycerol, and fatty acids into complex cellular lipids. Drug-treated cells recultured in drug-free medium regained their resistance to antibody-C mediated killing; these cells recovered their ability for complex lipid synthesis at this time. Thin layer chromatography of CHCl3:CH3OH lipid extracts from these cells indicated that the drug-induced increase in susceptibility to humoral immune attack correlated with the inhibition of acetate, glycerol, and fatty acid incorporation into cardiolipin and triglyceride in line-10 cells and the inhibition of incorporation of these compounds into cardiolipin alone in line-1 cells. No direct correlation was found between the sensitivity of the cells to humoral immune attack and the ability of the cells to incorporate precursors of lipid synthesis into other lipid moieties (sphyngomyelin, phosphatidyl serine, phosphatidyl choline, phosphatidyl glycerol, or cholesterol esters). The synthesis of cardiolipin and triglycerides, therefore, appears to be associated with the mechanism whereby these tumor cells resist antibody-C mediated killing.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D002308:Cardiolipins / Q000096:biosynthesis*; D005227:Fatty Acids / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006168:Guinea Pigs; D008113:Liver Neoplasms; D008297:Male; D014280:Triglycerides / Q000096:biosynthesis*
D000085:Acetates; D000903:Antibiotics, Antineoplastic; D002308:Cardiolipins; D005227:Fatty Acids; D014280:Triglycerides; D005990:Glycerol