Low density lipoprotein (LDL)-mediated suppression of Lewis lung carcinoma in hypercholesterolemic LDL receptor-deficient mice.
An inverse relationship has been reported between cancer risk and cholesterol level, prompting the hypothesis that hypercholesterolemia may be protective against cancer. We tested this hypothesis by evaluating the growth of Lewis lung carcinoma in three different murine models of hypercholesterolemia: Pluronic treated mice, apolipoprotein E (ApoE) deficient mice, and low density lipoprotein receptor (LDL-R) deficient mice. Only the accumulation of LDL-cholesterol in LDL-R deficient mice suppressed tumor growth. Accumulation of chylomicrons, very low density lipoproteins (VLDL), and cholesterol-enriched remnants in the Pluronic treated mice and ApoE deficient mice did not inhibit tumor growth, even though mice in all three models were equally hypercholesterolemic. Taken together, the experimental evidence from our studies indicate that high plasma cholesterol in the form of LDL-cholesterol could have a beneficial effect against cancer in vivo.
Trieu
V N
VN
Department of Cardiovascular Biology, Department of Molecular Epidemiology, Hughes Institute, St. Paul, Minnesota 55113, USA.
Uckun
F M
FM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000150:complications; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008078:Cholesterol, LDL; D006131:Growth Inhibitors; D011973:Receptors, LDL