Journal
ONCOTARGET
Volume 8, Issue 4, Pages 6433-6445Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.14118
Keywords
glucose addiction; platinum resistance; ovarian cancer; metabolism; autophagy
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Funding
- Italian Association for Cancer Research (AIRC) [N14032, N18803, IG14536]
- Italian Ministry of University and Research
- University of Padova [CPDA1325178]
- IOV 5 x1000 Intramural Grant
- AIRC
- Piscopia-Marie Curie fellowship
- IOV
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Deregulated glucose metabolism is observed in cancer but whether this metabolic trait influences response to or is modulated by cytotoxic drugs is unknown. We show here that tumor cells from epithelial ovarian cancer (EOC) patients can be categorized, according to their in vitro viability under glucose starvation, into glucose deprivation-sensitive (glucose-addicted, GA) and glucose deprivation-resistant (glucose non-addicted, GNA). When EOC cells were cultured in the absence of glucose, all samples from platinum (PLT)-sensitive patients felt into the GA group; they disclosed higher expression of glucose metabolism enzymes, higher proliferation rates and in vitro sensitivity to PLT. Moreover, GA patients showed reduced multi-drug resistance pump expression and autophagy, compared to GNA samples. The close association between PLT sensitivity and glucose metabolic profile was confirmed in a xenograft model, where a stringent parallelism between PLT sensitivity/resistance and glucose metabolism was identified. Finally, in a cohort of naive EOC patients categorized as GA or GNA at diagnosis, Kaplan Meier curves showed that the GA phenotype was associated with significantly better progression-free survival, compared to GNA patients.
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