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

Matteo Curtarello, Martina Tognon, Carolina Venturoli, Micol Silic-Benussi, Angela Grassi, Martina Verza, Sonia Minuzzo, Marica Pinazza, Valentina Brillo, Giovanni Tosi, Ruggero Ferrazza, Graziano Guella, Egidio Iorio, Adrien Godfroid, Nor Eddine Sounni, Alberto Amadori, Stefano Indraccolo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number1601
Pages (from-to)1-19
Number of pages19
JournalCells
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 9 2019

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  • Cite this

    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. (2019). Rewiring of Lipid Metabolism and Storage in Ovarian Cancer Cells after Anti-VEGF Therapy. Cells, 8(12), 1-19. [1601]. https://doi.org/10.3390/cells8121601