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Open AccessFeature PaperArticle

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

1
Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy
2
Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
3
Department of Biology, University of Padova, 35128 Padova, Italy
4
Department of Physics, University of Trento, Via Sommarive 14, 38123 Trento, Italy
5
Core Facilities, NMR and MRI Unit, Istituto Superiore di Sanità, 00161 Roma, Italy
6
Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liège, 4000 Liège, Belgium
*
Author to whom correspondence should be addressed.
The authors contributed equally to this work.
Cells 2019, 8(12), 1601; https://doi.org/10.3390/cells8121601
Received: 31 October 2019 / Revised: 2 December 2019 / Accepted: 6 December 2019 / Published: 9 December 2019
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Ovarian Cancer)
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. View Full-Text
Keywords: ovarian cancer; bevacizumab; metabolism; lipid droplets; LXR agonist ovarian cancer; bevacizumab; metabolism; lipid droplets; LXR agonist
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Curtarello, M.; Tognon, M.; Venturoli, C.; Silic-Benussi, M.; Grassi, A.; Verza, M.; Minuzzo, S.; Pinazza, M.; Brillo, V.; Tosi, G.; Ferrazza, R.; Guella, G.; Iorio, E.; Godfroid, A.; Sounni, N.E.; Amadori, A.; Indraccolo, S. Rewiring of Lipid Metabolism and Storage in Ovarian Cancer Cells after Anti-VEGF Therapy. Cells 2019, 8, 1601.

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