title: Resistance to glucose starvation as metabolic trait of platinum-resistant human epithelial ovarian cancer cells.
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 naïve 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.
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pastò
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pagotto
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pilotto
authors.affiliation: Istituto Oncologico Veneto IRCCS, Padova, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: De Paoli
authors.affiliation: Istituto Oncologico Veneto IRCCS, Padova, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: De Salvo
authors.affiliation: Istituto Oncologico Veneto IRCCS, Padova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baldoni
authors.affiliation: Istituto Oncologico Veneto IRCCS, Padova, Italy.
authors.forename: Maria Ornella
authors.initials: MO
authors.lastname: Nicoletto
authors.affiliation: Laboratory of Molecular Pharmacology, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.affiliation: Laboratory of Molecular Pharmacology, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Damia
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bellio
authors.affiliation: Istituto Oncologico Veneto IRCCS, Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.|Istituto Oncologico Veneto IRCCS, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Amadori
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000172:deficiency*; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016513:Mice, SCID; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D018797:Cell Cycle Proteins; D005947:Glucose; D027425:ATP-Binding Cassette, Sub-Family C Proteins
keywords: autophagy; glucose addiction; metabolism; ovarian cancer; platinum resistance