Resistance to glucose starvation as metabolic trait of platinum-resistant human epithelial ovarian cancer cells
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 gluc...
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| Veröffentlicht in: | Oncotarget 2017-01, Vol.8 (4), p.6433-6445 |
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| creator | Pastò, Anna Pagotto, Anna Pilotto, Giorgia De Paoli, Angela De Salvo, Gian Luca Baldoni, Alessandra Nicoletto, Maria Ornella Ricci, Francesca Damia, Giovanna Bellio, Chiara Indraccolo, Stefano Amadori, Alberto |
| description | 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. |
| doi_str_mv | 10.18632/oncotarget.14118 |
| format | Article |
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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.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.14118</identifier><identifier>PMID: 28031535</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Aged ; Animals ; Antineoplastic Agents - pharmacology ; Carboplatin - pharmacology ; Carcinoma, Ovarian Epithelial ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Enzymologic ; Glucose - deficiency ; Glycolysis - drug effects ; Humans ; Kaplan-Meier Estimate ; Mice, SCID ; Middle Aged ; Multidrug Resistance-Associated Proteins - genetics ; Multidrug Resistance-Associated Proteins - metabolism ; Neoplasms, Glandular and Epithelial - drug therapy ; Neoplasms, Glandular and Epithelial - genetics ; Neoplasms, Glandular and Epithelial - metabolism ; Neoplasms, Glandular and Epithelial - pathology ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Phenotype ; Research Paper ; Time Factors ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2017-01, Vol.8 (4), p.6433-6445</ispartof><rights>Copyright: © 2017 Pastò et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c286t-24372ed2eb4c4571bb38b4b01aaf3978979eeb07dbdfed2686332a9544b00d173</citedby><cites>FETCH-LOGICAL-c286t-24372ed2eb4c4571bb38b4b01aaf3978979eeb07dbdfed2686332a9544b00d173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351643/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351643/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28031535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pastò, Anna</creatorcontrib><creatorcontrib>Pagotto, Anna</creatorcontrib><creatorcontrib>Pilotto, Giorgia</creatorcontrib><creatorcontrib>De Paoli, Angela</creatorcontrib><creatorcontrib>De Salvo, Gian Luca</creatorcontrib><creatorcontrib>Baldoni, Alessandra</creatorcontrib><creatorcontrib>Nicoletto, Maria Ornella</creatorcontrib><creatorcontrib>Ricci, Francesca</creatorcontrib><creatorcontrib>Damia, Giovanna</creatorcontrib><creatorcontrib>Bellio, Chiara</creatorcontrib><creatorcontrib>Indraccolo, Stefano</creatorcontrib><creatorcontrib>Amadori, Alberto</creatorcontrib><title>Resistance to glucose starvation as metabolic trait of platinum-resistant human epithelial ovarian cancer cells</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>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.</description><subject>Aged</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Carboplatin - pharmacology</subject><subject>Carcinoma, Ovarian Epithelial</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Disease-Free Survival</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Glucose - deficiency</subject><subject>Glycolysis - drug effects</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Mice, SCID</subject><subject>Middle Aged</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Neoplasms, Glandular and Epithelial - drug therapy</subject><subject>Neoplasms, Glandular and Epithelial - genetics</subject><subject>Neoplasms, Glandular and Epithelial - metabolism</subject><subject>Neoplasms, Glandular and Epithelial - pathology</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Phenotype</subject><subject>Research Paper</subject><subject>Time Factors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctKAzEUDaKoqB_gRrJ0MzWv6cxsBBFfIAii65Bk7rSRzKQmmYJ_b2xrrdnccO855z4OQueUTGg95ezKD8YnFWaQJlRQWu-hY9qIpmBlyfd3_kfoLMYPkl8pqpo1h-iI1YTTkpfHyL9CtDGpwQBOHs_caHwEnDNhqZL1A1YR95CU9s4anIKyCfsOL1yuDmNfhA0_4fnYqwHDwqY5OKsc9ksVbE6ZH_WADTgXT9FBp1yEs008Qe_3d2-3j8Xzy8PT7c1zYVg9TQUTvGLQMtDCiLKiWvNaC02oUh1vqrqpGgBNqla3XYZN80E4U00pMoa0tOIn6Hqtuxh1D62BIY_u5CLYXoUv6ZWV_yuDncuZX8p8FToVPAtcbgSC_xwhJtnb-LOCGsCPUdK6FJRUgpEMpWuoCT7GAN22DSVy5ZX880quvMqci935toxfZ_g3GtKWUQ</recordid><startdate>20170124</startdate><enddate>20170124</enddate><creator>Pastò, Anna</creator><creator>Pagotto, Anna</creator><creator>Pilotto, Giorgia</creator><creator>De Paoli, Angela</creator><creator>De Salvo, Gian Luca</creator><creator>Baldoni, Alessandra</creator><creator>Nicoletto, Maria Ornella</creator><creator>Ricci, Francesca</creator><creator>Damia, Giovanna</creator><creator>Bellio, Chiara</creator><creator>Indraccolo, Stefano</creator><creator>Amadori, Alberto</creator><general>Impact Journals LLC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170124</creationdate><title>Resistance to glucose starvation as metabolic trait of platinum-resistant human epithelial ovarian cancer cells</title><author>Pastò, Anna ; Pagotto, Anna ; Pilotto, Giorgia ; De Paoli, Angela ; De Salvo, Gian Luca ; Baldoni, Alessandra ; Nicoletto, Maria Ornella ; Ricci, Francesca ; Damia, Giovanna ; Bellio, Chiara ; Indraccolo, Stefano ; Amadori, Alberto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c286t-24372ed2eb4c4571bb38b4b01aaf3978979eeb07dbdfed2686332a9544b00d173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Carboplatin - pharmacology</topic><topic>Carcinoma, Ovarian Epithelial</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Disease-Free Survival</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Resistance, Neoplasm</topic><topic>Female</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Glucose - deficiency</topic><topic>Glycolysis - drug effects</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Mice, SCID</topic><topic>Middle Aged</topic><topic>Multidrug Resistance-Associated Proteins - genetics</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>Neoplasms, Glandular and Epithelial - drug therapy</topic><topic>Neoplasms, Glandular and Epithelial - genetics</topic><topic>Neoplasms, Glandular and Epithelial - metabolism</topic><topic>Neoplasms, Glandular and Epithelial - pathology</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Phenotype</topic><topic>Research Paper</topic><topic>Time Factors</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Pastò, Anna</creatorcontrib><creatorcontrib>Pagotto, Anna</creatorcontrib><creatorcontrib>Pilotto, Giorgia</creatorcontrib><creatorcontrib>De Paoli, Angela</creatorcontrib><creatorcontrib>De Salvo, Gian Luca</creatorcontrib><creatorcontrib>Baldoni, Alessandra</creatorcontrib><creatorcontrib>Nicoletto, Maria Ornella</creatorcontrib><creatorcontrib>Ricci, Francesca</creatorcontrib><creatorcontrib>Damia, Giovanna</creatorcontrib><creatorcontrib>Bellio, Chiara</creatorcontrib><creatorcontrib>Indraccolo, Stefano</creatorcontrib><creatorcontrib>Amadori, Alberto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pastò, Anna</au><au>Pagotto, Anna</au><au>Pilotto, Giorgia</au><au>De Paoli, Angela</au><au>De Salvo, Gian Luca</au><au>Baldoni, Alessandra</au><au>Nicoletto, Maria Ornella</au><au>Ricci, Francesca</au><au>Damia, Giovanna</au><au>Bellio, Chiara</au><au>Indraccolo, Stefano</au><au>Amadori, Alberto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resistance to glucose starvation as metabolic trait of platinum-resistant human epithelial ovarian cancer cells</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-01-24</date><risdate>2017</risdate><volume>8</volume><issue>4</issue><spage>6433</spage><epage>6445</epage><pages>6433-6445</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><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.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28031535</pmid><doi>10.18632/oncotarget.14118</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Animals Antineoplastic Agents - pharmacology Carboplatin - pharmacology Carcinoma, Ovarian Epithelial Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Line, Tumor Cell Proliferation - drug effects Disease-Free Survival Dose-Response Relationship, Drug Drug Resistance, Neoplasm Female Gene Expression Regulation, Enzymologic Glucose - deficiency Glycolysis - drug effects Humans Kaplan-Meier Estimate Mice, SCID Middle Aged Multidrug Resistance-Associated Proteins - genetics Multidrug Resistance-Associated Proteins - metabolism Neoplasms, Glandular and Epithelial - drug therapy Neoplasms, Glandular and Epithelial - genetics Neoplasms, Glandular and Epithelial - metabolism Neoplasms, Glandular and Epithelial - pathology Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Phenotype Research Paper Time Factors Xenograft Model Antitumor Assays |
| title | Resistance to glucose starvation as metabolic trait of platinum-resistant human epithelial ovarian cancer cells |
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