Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma

dc.contributor.authorMerlos Rodrigo, Miguel Ángelcs
dc.contributor.authorMichálková, Hanacs
dc.contributor.authorStrmiska, Vladislavcs
dc.contributor.authorCasar, Bertacs
dc.contributor.authorCrespo, Pierocs
dc.contributor.authorDe los Rios, Viviancs
dc.contributor.authorCasal Álvarez, José Ignaciocs
dc.contributor.authorHaddad, Yazan Abdulmajeed Eyadhcs
dc.contributor.authorGuráň, Romancs
dc.contributor.authorEckschlager, Tomášcs
dc.contributor.authorPokorná, Petracs
dc.contributor.authorHeger, Zbyněkcs
dc.contributor.authorAdam, Vojtěchcs
dc.coverage.issue1cs
dc.coverage.volume11cs
dc.date.accessioned2021-05-06T14:55:32Z
dc.date.available2021-05-06T14:55:32Z
dc.date.issued2021-03-09cs
dc.description.abstractMetallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance. We confirmed the cisplatin-metallothionein complex formation using mass spectrometry. Overexpression of hMT3 decreased the sensitivity of neuroblastoma UKF-NB-4 cells to cisplatin. We report, for the first time, cisplatin-sensitive human UKF-NB-4 cells remodelled into cisplatin-resistant cells via high and constitutive hMT3 expression in an in vivo model using chick chorioallantoic membrane assay. Comparative proteomic analysis demonstrated that several biological pathways related to apoptosis, transport, proteasome, and cellular stress were involved in cisplatin-resistance in hMT3 overexpressing UKF-NB-4 cells. Overall, our data confirmed that up-regulation of hMT3 positively correlated with increased cisplatin-chemoresistance in neuroblastoma, and a high level of hMT3 could be one of the causes of frequent tumour relapses.en
dc.formattextcs
dc.format.extent1-14cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationScientific Reports. 2021, vol. 11, issue 1, p. 1-14.en
dc.identifier.doi10.1038/s41598-021-84185-xcs
dc.identifier.issn2045-2322cs
dc.identifier.other171008cs
dc.identifier.urihttp://hdl.handle.net/11012/196716
dc.language.isoencs
dc.publisherSpringer Naturecs
dc.relation"European Union (EU)" & "Horizon 2020"
dc.relation.ispartofScientific Reportscs
dc.relation.projectIdinfo:eu-repo/grantAgreement/EC/H2020/759585/EU//ToMeTuM
dc.relation.urihttps://www.nature.com/articles/s41598-021-84185-xcs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/2045-2322/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectMetallothionein-3en
dc.subjectcanceren
dc.subjectneuroblastomaen
dc.subjectcisplatinen
dc.subjectchemoresistanceen
dc.titleMetallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastomaen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-171008en
sync.item.dbtypeVAVen
sync.item.insts2021.05.06 16:55:32en
sync.item.modts2021.05.06 16:14:51en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Chytré nanonástrojecs
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