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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Metabolic alterations underlying Bevacizumab therapy in glioblastoma cells

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Miranda-Goncalves, Vera [1, 2] ; Cardoso-Carneiro, Diana [1, 2] ; Valbom, Ines [1, 2] ; Cury, Fernanda Paula [3] ; Silva, Viviane Aline [3] ; Granja, Sara [1, 2] ; Reis, Rui M. [1, 3, 2] ; Baltazar, Fatima [1, 2] ; Martinho, Olga [1, 3, 2]
Total Authors: 9
[1] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal
[2] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, Braga - Portugal
[3] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: ONCOTARGET; v. 8, n. 61, p. 103657-103670, NOV 28 2017.
Web of Science Citations: 4

Anti-VEGF therapy with Bevacizumab is approved for glioblastoma treatment, however, it is known that tumors acquired resistance and eventually became even more aggressive and infiltrative after treatment. In the present study we aimed to unravel the potential cellular mechanisms of resistance to Bevacizumab in glioblastoma in vitro models. Using a panel of glioblastoma cell lines we found that Bevacizumab is able to block the secreted VEGF by the tumor cells and be internalized to the cytoplasm, inducing cytotoxicity in vitro. We further found that Bevacizumab increases the expression of hypoxic HIF-1 alpha and CAIX) and glycolytic markers GLUT1 and MCT1), leading to higher glucose uptake and lactate production. Furthermore, we showed that part of the consumed glucose by the tumor cells can be stored as glycogen, hampering cell dead following Bevacizumab treatment. Importantly, we found that this change on the glycolytic metabolism occurs independently of hypoxia and before mitochondrial impairment or autophagy induction. Finally, the combination of Bevacizumab with glucose uptake inhibitors decreased in vivo tumor growth and angiogenesis and shift the expression of glycolytic proteins. In conclusion, we reported that Bevacizumab is able to increase the glucose metabolism on cancer cells by abrogating autocrine VEGF in vitro. Define the effects of anti-angiogenic drugs at the cellular level can allow us to discover ways to revert acquired resistance to this therapeutic approaches in the future. (AU)

FAPESP's process: 14/03684-0 - Functional role of kit GNNK+ and GNNK- isoforms in glioblastoma
Grantee:Fernanda de Paula Cury
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 15/02691-6 - Functional role of kit GNNK+ and GNNK- isoforms in glioblastoma
Grantee:Fernanda de Paula Cury
Support Opportunities: Scholarships abroad - Research Internship - Master's degree