Common biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells

Abstract Standard of care for Epithelial Ovarian Cancer (EOC) patients relies on platinum-based therapy. However, acquired resistance to platinum occurs frequently and predicts poor prognosis. To understand the mechanisms underlying acquired platinum-resistance, we have generated and characterized t...

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Autores principales:	Maura Sonego, Ilenia Pellizzari, Alessandra Dall’Acqua, Eliana Pivetta, Ilaria Lorenzon, Sara Benevol, Riccardo Bomben, Paola Spessotto, Roberto Sorio, Valter Gattei, Barbara Belletti, Monica Schiappacassi, Gustavo Baldassarre
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8bf1a13f3ec742d7ba5ce35739f9999f
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spelling	oai:doaj.org-article:8bf1a13f3ec742d7ba5ce35739f9999f2021-12-02T12:32:14ZCommon biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells10.1038/s41598-017-07005-12045-2322https://doaj.org/article/8bf1a13f3ec742d7ba5ce35739f9999f2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07005-1https://doaj.org/toc/2045-2322Abstract Standard of care for Epithelial Ovarian Cancer (EOC) patients relies on platinum-based therapy. However, acquired resistance to platinum occurs frequently and predicts poor prognosis. To understand the mechanisms underlying acquired platinum-resistance, we have generated and characterized three platinum-resistant isogenic EOC cell lines. Resistant cells showed 3-to 5- folds increase in platinum IC50. Cross-resistance to other chemotherapeutic agents commonly used in the treatment of EOC patients was variable and dependent on the cell line utilized. Gene expression profiling (GEP) of coding and non-coding RNAs failed to identify a common signature that could collectively explain the mechanism of resistance. However, we observed that all resistant cell lines displayed a decreased level of DNA platination and a faster repair of damaged DNA. Furthermore, all platinum resistant cell lines displayed a change in their morphology and a higher ability to grown on mesothelium. Overall, we have established and characterized three new models of platinum-resistant EOC cell lines that could be exploited to further dissect the molecular mechanisms underlying acquired resistance to platinum. Our work also suggests that GEP studies alone, at least when performed under basal culture condition, do not represent the optimal way to identify molecular alterations linked to DNA repair pathway defects.Maura SonegoIlenia PellizzariAlessandra Dall’AcquaEliana PivettaIlaria LorenzonSara BenevolRiccardo BombenPaola SpessottoRoberto SorioValter GatteiBarbara BellettiMonica SchiappacassiGustavo BaldassarreNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maura Sonego Ilenia Pellizzari Alessandra Dall’Acqua Eliana Pivetta Ilaria Lorenzon Sara Benevol Riccardo Bomben Paola Spessotto Roberto Sorio Valter Gattei Barbara Belletti Monica Schiappacassi Gustavo Baldassarre Common biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells
description	Abstract Standard of care for Epithelial Ovarian Cancer (EOC) patients relies on platinum-based therapy. However, acquired resistance to platinum occurs frequently and predicts poor prognosis. To understand the mechanisms underlying acquired platinum-resistance, we have generated and characterized three platinum-resistant isogenic EOC cell lines. Resistant cells showed 3-to 5- folds increase in platinum IC50. Cross-resistance to other chemotherapeutic agents commonly used in the treatment of EOC patients was variable and dependent on the cell line utilized. Gene expression profiling (GEP) of coding and non-coding RNAs failed to identify a common signature that could collectively explain the mechanism of resistance. However, we observed that all resistant cell lines displayed a decreased level of DNA platination and a faster repair of damaged DNA. Furthermore, all platinum resistant cell lines displayed a change in their morphology and a higher ability to grown on mesothelium. Overall, we have established and characterized three new models of platinum-resistant EOC cell lines that could be exploited to further dissect the molecular mechanisms underlying acquired resistance to platinum. Our work also suggests that GEP studies alone, at least when performed under basal culture condition, do not represent the optimal way to identify molecular alterations linked to DNA repair pathway defects.
format	article
author	Maura Sonego Ilenia Pellizzari Alessandra Dall’Acqua Eliana Pivetta Ilaria Lorenzon Sara Benevol Riccardo Bomben Paola Spessotto Roberto Sorio Valter Gattei Barbara Belletti Monica Schiappacassi Gustavo Baldassarre
author_facet	Maura Sonego Ilenia Pellizzari Alessandra Dall’Acqua Eliana Pivetta Ilaria Lorenzon Sara Benevol Riccardo Bomben Paola Spessotto Roberto Sorio Valter Gattei Barbara Belletti Monica Schiappacassi Gustavo Baldassarre
author_sort	Maura Sonego
title	Common biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells
title_short	Common biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells
title_full	Common biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells
title_fullStr	Common biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells
title_full_unstemmed	Common biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells
title_sort	common biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8bf1a13f3ec742d7ba5ce35739f9999f
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Common biological phenotypes characterize the acquisition of platinum-resistance in epithelial ovarian cancer cells

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