title: Tumor-Induced Hyperlipidemia Contributes to Tumor Growth.
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.
authors.affiliation: Institute of Pathology, Medical University of Graz, 8010 Graz, Austria; Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB T6G 2R3, Canada.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Huang
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB T6G 2R3, Canada; Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada.
authors.forename: Lena
authors.initials: L
authors.lastname: Li
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB T6G 2R3, Canada; Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada.
authors.forename: Jihong
authors.initials: J
authors.lastname: Lian
authors.affiliation: Institute of Pathology, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schauer
authors.affiliation: Institute of Pathology, Medical University of Graz, 8010 Graz, Austria; Institute of Molecular Biosciences, Karl Franzens University of Graz, 8010 Graz, Austria.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Vesely
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kratky
authors.affiliation: Institute of Pathology, Medical University of Graz, 8010 Graz, Austria. Electronic address: gerald.hoefler@medunigraz.at.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB T6G 2R3, Canada; Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada. Electronic address: richard.lehner@ualberata.ca.
authors.forename: Richard
authors.initials: R
authors.lastname: Lehner
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D002914:Chylomicrons / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism / Q000473:pathology*; D007328:Insulin / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D000071449:Proprotein Convertase 9 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002914:Chylomicrons; D007328:Insulin; D008079:Lipoproteins, VLDL; D016044:Fusion Proteins, bcr-abl; D002265:Carboxylic Ester Hydrolases; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9