{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:06:48Z","timestamp":1785431208574,"version":"3.56.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["DIAG"],"award-info":[{"award-number":["DIAG"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00c3 Cesk\u00c3\u00a9 Republiky","doi-asserted-by":"publisher","award":["UHHK, 00179906"],"award-info":[{"award-number":["UHHK, 00179906"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The transcriptional alterations underlying epithelial-to-mesenchymal transition (EMT) in chemoresistant ovarian cancer remain a matter of debate, with emerging evidence pointing to tumour cell plasticity and subclone reprogramming. In this study, we developed a cisplatin-tolerant ovarian cancer model by treating the cisplatin-sensitive OVCAR-3 cell line with a single dose of cisplatin, generating the OVCAR-3 CP variant. These cisplatin-tolerant cells exhibited distinct EMT-related changes at both transcriptomic and protein levels, potentially regulated by epigenetic mechanisms. EMT profiling revealed that OVCAR-3 CP cells did not display a pronounced mesenchymal phenotype but rather retained epithelial characteristics and showed elevated expression of\n                    <jats:italic>ALDH3A1<\/jats:italic>\n                    . In contrast, the parental chemosensitive OVCAR-3 cells expressed canonical mesenchymal markers (\n                    <jats:italic>CDH2, VIM, ZEB1\/2, SNAIL, SLUG<\/jats:italic>\n                    ) and lacked stemness marker expression. Upon xenografting, both OVCAR-3 and OVCAR-3 CP cells demonstrated phenotypic plasticity, with parental OVCAR-3 xenografts acquiring EMT-like features resembling to those observed in cisplatin-tolerant tumours. These findings suggest a decoupling of EMT from cisplatin-tolerance and instead underscore a stronger association between stemness traits and cisplatin tolerance. Our data further indicate that xenografting can induce significant cellular reprogramming. Comprehensive characterization of ovarian cancer cell-derived xenograft is therefore essential, as they represent a valuable translational platform for investigating therapy adapted ovarian cancer cells.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0342326","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T18:30:37Z","timestamp":1770316237000},"page":"e0342326","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stemness and EMT profiles shift in xenografts derived from cisplatin-sensitive and cisplatin-tolerant ovarian cancer cells"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7802-5564","authenticated-orcid":true,"given":"Alena","family":"Mrkvicova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7891-9979","authenticated-orcid":true,"given":"Marcela","family":"Slavickova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Peterova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Melounkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-4140","authenticated-orcid":true,"given":"Helena","family":"Parova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radim","family":"Havelek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3203-856X","authenticated-orcid":true,"given":"Anna","family":"Krejcova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Kohlerova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2861-5483","authenticated-orcid":true,"given":"Jana","family":"Nekvindova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Kazimirova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Hajzlerova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Rozko\u0161","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5370-2290","authenticated-orcid":true,"given":"Martina","family":"Rezacova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"issue":"2","key":"pone.0342326.ref001","first-page":"172","article-title":"Cisplatin resistance: preclinical findings and clinical implications","volume":"1806","author":"B K\u00f6berle","year":"2010","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"pone.0342326.ref002","article-title":"Chemoresistance in ovarian cancer: exploiting cancer stem cell metabolism","volume":"29","author":"SS Li","year":"2018","journal-title":"J Gynecol Oncol"},{"issue":"4","key":"pone.0342326.ref003","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s00018-018-2954-1","article-title":"Comprehensive review on how platinum- and taxane-based chemotherapy of ovarian cancer affects biology of normal cells","volume":"76","author":"J Miku\u0142a-Pietrasik","year":"2019","journal-title":"Cell Mol Life Sci"},{"issue":"5","key":"pone.0342326.ref004","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3892\/or.2022.8313","article-title":"Tumor microenvironment manipulates chemoresistance in ovarian cancer (Review)","volume":"47","author":"Q Zhang","year":"2022","journal-title":"Oncol Rep"},{"issue":"1","key":"pone.0342326.ref005","doi-asserted-by":"crossref","first-page":"10048","DOI":"10.1038\/s41467-025-66376-6","article-title":"Drug-tolerant persister cells in cancer: bridging the gaps between bench and bedside","volume":"16","author":"Z Wang","year":"2025","journal-title":"Nat Commun"},{"issue":"7974","key":"pone.0342326.ref006","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41586-023-06342-8","article-title":"Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells","volume":"620","author":"Y Goyal","year":"2023","journal-title":"Nature"},{"issue":"7579","key":"pone.0342326.ref007","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nature16064","article-title":"Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer","volume":"527","author":"X Zheng","year":"2015","journal-title":"Nature"},{"issue":"3","key":"pone.0342326.ref008","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.apsb.2019.03.001","article-title":"Targeting slug-mediated non-canonical activation of c-Met to overcome chemo-resistance in metastatic ovarian cancer cells","volume":"9","author":"L Chang","year":"2019","journal-title":"Acta Pharm Sin B"},{"issue":"3","key":"pone.0342326.ref009","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.3892\/or.2017.5834","article-title":"Snail maintains metastatic potential, cancer stem-like properties, and chemoresistance in mesenchymal mouse breast cancer TUBO\u2011P2J cells","volume":"38","author":"SY Ma","year":"2017","journal-title":"Oncol Rep"},{"issue":"59","key":"pone.0342326.ref010","doi-asserted-by":"crossref","first-page":"99482","DOI":"10.18632\/oncotarget.20107","article-title":"Inhibition of ZEB1 leads to inversion of metastatic characteristics and restoration of paclitaxel sensitivity of chronic chemoresistant ovarian carcinoma cells","volume":"8","author":"J Sakata","year":"2017","journal-title":"Oncotarget"},{"issue":"7579","key":"pone.0342326.ref011","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nature15748","article-title":"Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance","volume":"527","author":"KR Fischer","year":"2015","journal-title":"Nature"},{"issue":"6","key":"pone.0342326.ref012","doi-asserted-by":"crossref","first-page":"5007","DOI":"10.3892\/ol.2016.5342","article-title":"Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail","volume":"12","author":"S Fang","year":"2016","journal-title":"Oncol Lett"},{"issue":"6","key":"pone.0342326.ref013","article-title":"DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma","volume":"13","author":"XS Chen","year":"2021","journal-title":"Cancers"},{"issue":"10","key":"pone.0342326.ref014","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines10102482","article-title":"Interplay between partial EMT and cisplatin resistance as the drivers for recurrence in HNSCC","volume":"10","author":"J Ingruber","year":"2022","journal-title":"Biomedicines"},{"issue":"5","key":"pone.0342326.ref015","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.7150\/thno.46460","article-title":"Cisplatin prevents breast cancer metastasis through blocking early EMT and retards cancer growth together with paclitaxel","volume":"11","author":"H Wang","year":"2021","journal-title":"Theranostics"},{"issue":"4","key":"pone.0342326.ref016","doi-asserted-by":"crossref","first-page":"915","DOI":"10.4143\/crt.2016.322","article-title":"Patient-derived xenograft models of epithelial ovarian cancer for preclinical studies","volume":"49","author":"EJ Heo","year":"2017","journal-title":"Cancer Res Treat"},{"issue":"1","key":"pone.0342326.ref017","doi-asserted-by":"crossref","first-page":"6314","DOI":"10.1038\/s41598-019-42680-2","article-title":"Gene expression differences between matched pairs of ovarian cancer patient tumors and patient-derived xenografts","volume":"9","author":"Y Liu","year":"2019","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0342326.ref018","first-page":"850","article-title":"Increased platinum-DNA damage tolerance is associated with cisplatin resistance and cross-resistance to various chemotherapeutic agents in unrelated human ovarian cancer cell lines","volume":"57","author":"SW Johnson","year":"1997","journal-title":"Cancer Res"},{"issue":"3","key":"pone.0342326.ref019","doi-asserted-by":"crossref","first-page":"183503","DOI":"10.1016\/j.bbamem.2020.183503","article-title":"Role of tight junctions in the epithelial-to-mesenchymal transition of cancer cells","volume":"1863","author":"D Kyuno","year":"2021","journal-title":"Biochim Biophys Acta Biomembr"},{"key":"pone.0342326.ref020","doi-asserted-by":"crossref","first-page":"807862","DOI":"10.3389\/fcell.2021.807862","article-title":"Integrated analysis of ferroptosis-related biomarker signatures to improve the diagnosis and prognosis prediction of ovarian cancer","volume":"9","author":"H Wang","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"pone.0342326.ref021","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cell.2010.02.027","article-title":"A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations","volume":"141","author":"SV Sharma","year":"2010","journal-title":"Cell"},{"issue":"7658","key":"pone.0342326.ref022","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature22794","article-title":"Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance","volume":"546","author":"SM Shaffer","year":"2017","journal-title":"Nature"},{"issue":"2","key":"pone.0342326.ref023","first-page":"1595","article-title":"NOS1 upregulates ABCG2 expression contributing to DDP chemoresistance in ovarian cancer cells","volume":"17","author":"X Li","year":"2019","journal-title":"Oncol Lett"},{"issue":"7","key":"pone.0342326.ref024","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1517\/17425250902973711","article-title":"Pharmacogenomics of platinum-based chemotherapy in NSCLC","volume":"5","author":"MAT Hildebrandt","year":"2009","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"17","key":"pone.0342326.ref025","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.3390\/ijms20174136","article-title":"New insights into mechanisms of cisplatin resistance: from tumor cell to microenvironment","volume":"20","author":"S-H Chen","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pone.0342326.ref026","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s00428-005-1228-0","article-title":"Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients","volume":"447","author":"P Surowiak","year":"2005","journal-title":"Virchows Arch"},{"issue":"1","key":"pone.0342326.ref027","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/jnc.14250","article-title":"Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis","volume":"144","author":"Z Zhu","year":"2018","journal-title":"J Neurochem"},{"issue":"9","key":"pone.0342326.ref028","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/jnci\/82.9.749","article-title":"Analysis of events associated with cell cycle arrest at G2 phase and cell death induced by cisplatin","volume":"82","author":"CM Sorenson","year":"1990","journal-title":"J Natl Cancer Inst"},{"issue":"3","key":"pone.0342326.ref029","doi-asserted-by":"crossref","first-page":"956","DOI":"10.4143\/crt.2017.181","article-title":"Comparison of clinical features and outcomes in epithelial ovarian cancer according to tumorigenicity in patient-derived xenograft models","volume":"50","author":"KJ Eoh","year":"2018","journal-title":"Cancer Res Treat"},{"key":"pone.0342326.ref030","doi-asserted-by":"crossref","first-page":"744256","DOI":"10.3389\/fonc.2021.744256","article-title":"Patient-Derived Xenografts Are a Reliable Preclinical Model for the Personalized Treatment of Epithelial Ovarian Cancer","volume":"11","author":"J Chen","year":"2021","journal-title":"Front Oncol"},{"issue":"1","key":"pone.0342326.ref031","article-title":"What is new in cancer-associated fibroblast biomarkers?","volume":"21","author":"ZH Zhao","year":"2023","journal-title":"Cell Commun Signal"},{"issue":"12","key":"pone.0342326.ref032","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.prp.2015.09.005","article-title":"Investigation of the origin of stromal and endothelial cells at the desmoplastic interface in xenograft tumor in mice","volume":"211","author":"M Jung","year":"2015","journal-title":"Pathol Res Pract"},{"issue":"5","key":"pone.0342326.ref033","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.ajpath.2015.01.016","article-title":"Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through incorporation of murine stromal elements","volume":"185","author":"D Delitto","year":"2015","journal-title":"Am J Pathol"},{"issue":"11","key":"pone.0342326.ref034","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1038\/ng.3967","article-title":"Patient-derived xenografts undergo mouse-specific tumor evolution","volume":"49","author":"U Ben-David","year":"2017","journal-title":"Nat Genet"},{"issue":"6","key":"pone.0342326.ref035","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41580-020-0237-9","article-title":"Guidelines and definitions for research on epithelial-mesenchymal transition","volume":"21","author":"J Yang","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"20","key":"pone.0342326.ref036","doi-asserted-by":"crossref","first-page":"7613","DOI":"10.3390\/ijms21207613","article-title":"Establishment of acquired cisplatin resistance in ovarian cancer cell lines characterized by enriched metastatic properties with increased twist expression","volume":"21","author":"E Bahar","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"10","key":"pone.0342326.ref037","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1002\/jcb.23199","article-title":"Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile","volume":"112","author":"A Latifi","year":"2011","journal-title":"J Cell Biochem"},{"key":"pone.0342326.ref038","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/1471-2407-12-91","article-title":"EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer","volume":"12","author":"AM Haslehurst","year":"2012","journal-title":"BMC Cancer"},{"issue":"15","key":"pone.0342326.ref039","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1038\/onc.2014.136","article-title":"Epithelial-mesenchymal status renders differential responses to cisplatin in ovarian cancer","volume":"34","author":"QH Miow","year":"2015","journal-title":"Oncogene"},{"issue":"9","key":"pone.0342326.ref040","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/jnci\/djn123","article-title":"Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy","volume":"100","author":"X Li","year":"2008","journal-title":"J Natl Cancer Inst"},{"issue":"2","key":"pone.0342326.ref041","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1158\/0008-5472.CAN-20-1488","article-title":"Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis","volume":"81","author":"Y Wang","year":"2021","journal-title":"Cancer Res"},{"issue":"1","key":"pone.0342326.ref042","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/ijc.25967","article-title":"Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells","volume":"130","author":"I Kryczek","year":"2012","journal-title":"Int J Cancer"},{"issue":"3","key":"pone.0342326.ref043","first-page":"684","article-title":"Cancer stem cells, epithelial-mesenchymal transition, ATP and their roles in drug resistance in cancer","volume":"4","author":"H Zhang","year":"2021","journal-title":"Cancer Drug Resist"},{"issue":"11","key":"pone.0342326.ref044","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1093\/bioinformatics\/18.11.1427","article-title":"MethPrimer: designing primers for methylation PCRs","volume":"18","author":"L-C Li","year":"2002","journal-title":"Bioinformatics"},{"issue":"1","key":"pone.0342326.ref045","first-page":"1","article-title":"FactoMineR: an r package for multivariate analysis","volume":"25","author":"S Le","year":"2008","journal-title":"J Stat Softw"},{"key":"pone.0342326.ref046","unstructured":"Kassambara A, Mundt F. Factoextra: Extract and Visualize the Results of Multivariate Data Analyses. R Package Version 1.0.7. https:\/\/CRAN.R-project.org\/package=factoextra 2020."}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0342326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T18:30:44Z","timestamp":1770316244000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0342326"}},"subtitle":[],"editor":[{"given":"Eric","family":"Asselin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0342326","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,5]]}}}