Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Huang, J; Li, L; Lian, J; Schauer, S; Vesely, PW; Kratky, D; Hoefler, G; Lehner, R.
Tumor-Induced Hyperlipidemia Contributes to Tumor Growth.
Cell Rep. 2016; 15(2): 336-348. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Hoefler Gerald
Huang Jianfeng
Kratky Dagmar
Schauer Silvia
Vesely Paul
Gendermonitor:
Altmetrics:

Number of Figures: 7
| | | | | | |
Abstract:
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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

© Meduni Graz Impressum