The lipid composition of Yoshida ascites hepatoma cells was analyzed together with that of ascitic plasma and of livers and blood plasma from host and normal rats. In comparison to normal livers, host livers showed no significant differences in the content of the various lipid classes, but contained a higher percentage of palmitic acid and a lower proportion of arachidonic acid in the major phospholipid classes. In addition, tumor growth induced a marked hypertriglyceridemia in host animals; changes in the concentration of other plasma lipid classes were not statistically significant. The ascitic plasma contained small amounts of lipids mainly constituted by cholesteryl esters and phospholipids. Yoshida hepatoma cells contained less phospholipids in comparison to both host and normal liver, while the increased level of triglycerides and the decrease of free fatty acids were not statistically significant. Hepatoma cells showed appreciable amounts of ether-linked lipids associated in part to neutral lipids (as glyceryl ether diesters) and, in part, to ethanolamine and choline phosphoglycerides. The alkyl groups in GEDE as well as in ethanolamine and choline phosphoglycerides were mainly constituted by C16:0 and C18:0 followed by C18:1. The alk-1-enyl groups in ethanolamine and choline phosphoglycerides were C16:0 and C18:0 with only a minor proportion of C18:1. In comparison to both host and normal liver, Yoshida hepatoma cells showed significant changes in the fatty acid composition of neutral lipids and phospholipids. Some of the major changes consisted of an increase of monoenoic acids associated with a decrease of arachidonic and docosahexaenoic acids in phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol.

Lipid components influence several cell surface properties that are critical in different stages of the metastatic process. In this study, we examined whether the different lung-colonizing potential of B16-F1 and B16-F10 melanoma cells could be related to a characteristic lipid profile. The lipid analyses, carried out on the same cell cultures used for the assay of lung-colonizing potential, revealed characteristics in the lipid composition of both B16-F1 and B16-F10 melanoma cells that are common to other systems of malignant cells: a high level of 18:1 associated with low proportions of polyunsaturated fatty acids in phospholipids, accumulation of ether-linked lipids and absence of complex gangliosides. The two B16 melanoma variants differed significantly only with respect to ether-linked lipids, due to a higher level of alkyl-PC in B16-F10 than in B16-F1.

To determine whether a metastatic phenotype may be correlated with a characteristic lipid pattern, we compared the lipid composition of low metastasizing Balb/c 3T3 cells transformed by the B77 strain of Rous sarcoma virus (B77-3T3 cells) with that of a subclone isolated by growth in 0.6% agar, the B77-AA6 cells, which exhibit a high capacity for spontaneous metastasis. B77-3T3 cells revealed characteristics in their lipid composition common to other systems of transformed cells, i.e., an accumulation of ether-linked lipids, a reduction of the more complex gangliosides, an increase of oleic acid (18:1) and a decrease of arachidonic (20:4) and C22 polyunsaturated fatty acids in phospholipids. High metastatic B77-AA6 cells showed: a) an even more marked decrease of complex gangliosides; b) a more pronounced increase of 18:1 and decrease of 20:4 and 22 polyunsaturated fatty acids in certain phospholipid classes; and c) a higher percentage of alkyl-acyl subfractions in both phosphatidylcholine and phosphatidylethanolamine than B77-3T3 cells. Comparing the data for other systems of metastatic cells with those of lipid studies of spontaneously metastasizing B77-AA6 cell system leads us to conclude that the metastatic phenotype is characterized by a change in ether-linked lipids, rather than in fatty acids.

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