Alterations in biosynthesis and homeostasis of cholesterol and in lipoprotein patterns in mice bearing a transplanted lymphoid tumor.
The membrane fluidity of murine lymphoid GRSL tumor cells has been shown to depend on their site of growth in the host. Tumor cells located in ascites, in contrast to those in the enlarged spleen, show a very high plasma membrane fluidity, mainly due to a decreased level of cellular (membrane) cholesterol. Yet, the rate of cholesterol biosynthesis in the tumor cells as estimated by the activity of HMG-CoA reductase and the incorporation of [14C]acetate into cholesterol was extremely high when compared to various lymphoid cells in normal control mice. Also the rate of biosynthesis and the cholesterol content in liver and spleen of tumor-bearing mice were substantially higher than in the organs of control mice. Blood plasma cholesterol, however, was decreased in tumor-bearing mice as a result of altered lipoprotein patterns. Outgrowth of the tumor was accompanied by a strong reduction in plasma high-density lipoproteins. Low-density lipoproteins became transiently increased, but eventually all lipoproteins, and consequently the plasma cholesterol content decreased to very low levels, especially so in the ascites plasma. The low transfer of [14C]cholesteryl ester-labeled lipoproteins between blood and ascites plasma after either intravenous or intraperitoneal injection suggested a hampered flow between the two compartments. Also apparent differences in cholesteryl ester fatty acid composition between lipoproteins of the blood and ascites plasma indicated the lack of a rapid equilibration between the two compartments. The results suggest that the limited availability of lipoproteins as an additional source of cholesterol to the rapidly growing ascites cells promotes their high membrane fluidity.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001201:Ascites / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis; D006706:Homeostasis; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007942:Leukemia, Experimental / Q000097:blood / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000502:physiology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D000085:Acetates; D005227:Fatty Acids; D008074:Lipoproteins; D008563:Membrane Lipids; D009363:Neoplasm Proteins; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases