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

[en] 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 e ects of bevacizumab.

Disciplines :

Oncology

Author, co-author :

Curtarello, Matteo

Tognon, Martina

Venturoli, Carolina

Silic-Benussi, Micol

Grassi, Angela

Verza, Martina

Minuzzo, Sonia

Pinazza, Marica

Brillo, Valentina

Tosi, Giovanni

More authors (7 more)

Language :

English

Title :

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

Publication date :

2019

Journal title :

Cells

eISSN :

2073-4409

Publisher :

Multidisciplinary Digital Publishing Institute (MDPI), Basel, Switzerland

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 18 December 2019

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