Tumor-Induced Hyperlipidemia Contributes to Tumor Growth.

Citation data:

Cell reports, ISSN: 2211-1247, Vol: 15, Issue: 2, Page: 336-48

Publication Year:
2016
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PMID:
27050512
DOI:
10.1016/j.celrep.2016.03.020; 10.3410/f.726267979.793543442
PMCID:
PMC4984953
Author(s):
Huang, Jianfeng; Li, Lena; Lian, Jihong; Schauer, Silvia; Vesely, Paul W; Kratky, Dagmar; Hoefler, Gerald; Lehner, Richard
Publisher(s):
Faculty of 1000, Ltd.; Elsevier BV
Tags:
Biochemistry, Genetics and Molecular Biology
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article description
The known link between obesity and cancer suggests an important interaction between the host lipid metabolism and tumorigenesis. Here, we used a syngeneic tumor graft model to demonstrate that tumor development influences the host lipid metabolism. BCR-Abl-transformed precursor B cell tumors induced hyperlipidemia by stimulating very low-density lipoprotein (VLDL) production and blunting VLDL and low-density lipoprotein (LDL) turnover. To assess whether tumor progression was dependent on tumor-induced hyperlipidemia, we utilized the VLDL production-deficient mouse model, carboxylesterase3/triacylglycerol hydrolase (Ces3/TGH) knockout mice. In Ces3/Tgh(-/-) tumor-bearing mice, plasma triglyceride and cholesterol levels were attenuated. Importantly tumor weight was reduced in Ces3/Tgh(-/-) mice. Mechanistically, reduced tumor growth in Ces3/Tgh(-/-) mice was attributed to reversal of tumor-induced PCSK9-mediated degradation of hepatic LDLR and decrease of LDL turnover. Our data demonstrate that tumor-induced hyperlipidemia encompasses a feed-forward loop that reprograms hepatic lipoprotein homeostasis in part by providing LDL cholesterol to support tumor growth.