Rewiring of Lipid Metabolism and Storage in Ovarian Cancer Cells after Anti-VEGF Therapy

Anti-angiogenic therapy triggers metabolic alterations in experimental and human tumors, the best characterized being exacerbated glycolysis and lactate production. By using both Liquid Chromatography-Mass Spectrometry (LC-MS) and Nuclear Magnetic Resonance (NMR) analysis, we found that treatment of...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2019-12, Vol.8 (12), p.1601
Main Authors: Curtarello, Matteo, Tognon, Martina, Venturoli, Carolina, Silic-Benussi, Micol, Grassi, Angela, Verza, Martina, Minuzzo, Sonia, Pinazza, Marica, Brillo, Valentina, Tosi, Giovanni, Ferrazza, Ruggero, Guella, Graziano, Iorio, Egidio, Godfroid, Adrien, Sounni, Nor Eddine, Amadori, Alberto, Indraccolo, Stefano
Format: Article
Language:English
Subjects:
Acidosis
Agonists
Angiogenesis
Angiogenèse
Antigens
Bevacizumab
Cancer therapies
Cell viability
Fatty acids
Glycolysis
Human health sciences
Hypoxia
Kinases
Lactic acid
Lipid metabolism
Lipids
Liquid chromatography
Liver X receptors
Mass spectroscopy
Metabolism
Monoclonal antibodies
Métabolisme
NMR
Nuclear magnetic resonance
Oncologie
Oncology
Ovarian cancer
Resistance
Sciences de la santé humaine
Solvents
Transcriptomes
Tumors
Vascular endothelial growth factor
Xenografts
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Summary:Anti-angiogenic therapy triggers metabolic alterations in experimental and human tumors, the best characterized being exacerbated glycolysis and lactate production. By using both Liquid Chromatography-Mass Spectrometry (LC-MS) and Nuclear Magnetic Resonance (NMR) analysis, we found that treatment of ovarian cancer xenografts with the anti-Vascular Endothelial Growth Factor (VEGF) neutralizing antibody bevacizumab caused marked alterations of the tumor lipidomic profile, including increased levels of triacylglycerols and reduced saturation of lipid chains. Moreover, transcriptome analysis uncovered up-regulation of pathways involved in lipid metabolism. These alterations were accompanied by increased accumulation of lipid droplets in tumors. This phenomenon was reproduced under hypoxic conditions in vitro, where it mainly depended from uptake of exogenous lipids and was counteracted by treatment with the Liver X Receptor (LXR)-agonist GW3965, which inhibited cancer cell viability selectively under reduced serum conditions. This multi-level analysis indicates alterations of lipid metabolism following anti-VEGF therapy in ovarian cancer xenografts and suggests that LXR-agonists might empower anti-tumor effects of bevacizumab.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells8121601