Resistance to glucose starvation as metabolic trait of platinum-resistant human epithelial ovarian cancer cells
| Autor: | Gian Luca De Salvo, Angela De Paoli, Anna Pagotto, Chiara Bellio, Anna Pastò, Francesca Ricci, Giovanna Damia, Alberto Amadori, Giorgia Pilotto, Alessandra Baldoni, Stefano Indraccolo, Maria Ornella Nicoletto |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Enzymologic
0301 basic medicine Oncology Time Factors Drug Resistance Cell Cycle Proteins Kaplan-Meier Estimate Mice SCID Carcinoma Ovarian Epithelial Carboplatin Mice Ovarian Epithelial Neoplasms Cytotoxic T cell Neoplasms Glandular and Epithelial chemistry.chemical_classification Ovarian Neoplasms Tumor Glandular and Epithelial Middle Aged platinum resistance ovarian cancer Phenotype glucose addiction Female Drug Multidrug Resistance-Associated Proteins Glycolysis Research Paper medicine.medical_specialty autophagy Autophagy Glucose addiction Metabolism Ovarian cancer Platinum resistance Aged Animals Antineoplastic Agents Cell Line Tumor Cell Proliferation Disease-Free Survival Dose-Response Relationship Drug Gene Expression Regulation Enzymologic Glucose Humans Xenograft Model Antitumor Assays Drug Resistance Neoplasm Carbohydrate metabolism SCID Cell Line Dose-Response Relationship 03 medical and health sciences Internal medicine medicine business.industry Carcinoma Cancer medicine.disease In vitro 030104 developmental biology Enzyme Endocrinology Gene Expression Regulation chemistry Neoplasm business metabolism |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Anna Pasto 1 , Anna Pagotto 1 , Giorgia Pilotto 1 , Angela De Paoli 2 , Gian Luca De Salvo 2 , Alessandra Baldoni 2 , Maria Ornella Nicoletto 2 , Francesca Ricci 3 , Giovanna Damia 3 , Chiara Bellio 1 , Stefano Indraccolo 2, * , Alberto Amadori 1, 2, * 1 Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy 2 Istituto Oncologico Veneto IRCCS, Padova, Italy 3 Laboratory of Molecular Pharmacology, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy * These authors contributed equally to this work Correspondence to: Stefano Indraccolo, email: stefano.indraccolo@unipd.it Anna Pasto, email: annapasto.phd@gmail.com Keywords: glucose addiction, platinum resistance, ovarian cancer, metabolism, autophagy Received: August 31, 2016 Accepted: December 15, 2016 Published: December 23, 2016 ABSTRACT 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. |
| Databáze: | OpenAIRE |
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