Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma

Abstract Metallothionein-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...

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Autores principales:	Miguel Angel Merlos Rodrigo, Hana Michalkova, Vladislav Strmiska, Berta Casar, Piero Crespo, Vivian de los Rios, J. Ignacio Casal, Yazan Haddad, Roman Guran, Tomas Eckschlager, Petra Pokorna, Zbynek Heger, Vojtech Adam
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c380e720965d4d49b73aadef566e6723
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spelling	oai:doaj.org-article:c380e720965d4d49b73aadef566e67232021-12-02T13:34:46ZMetallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma10.1038/s41598-021-84185-x2045-2322https://doaj.org/article/c380e720965d4d49b73aadef566e67232021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84185-xhttps://doaj.org/toc/2045-2322Abstract Metallothionein-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.Miguel Angel Merlos RodrigoHana MichalkovaVladislav StrmiskaBerta CasarPiero CrespoVivian de los RiosJ. Ignacio CasalYazan HaddadRoman GuranTomas EckschlagerPetra PokornaZbynek HegerVojtech AdamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Miguel Angel Merlos Rodrigo Hana Michalkova Vladislav Strmiska Berta Casar Piero Crespo Vivian de los Rios J. Ignacio Casal Yazan Haddad Roman Guran Tomas Eckschlager Petra Pokorna Zbynek Heger Vojtech Adam Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma
description	Abstract Metallothionein-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.
format	article
author	Miguel Angel Merlos Rodrigo Hana Michalkova Vladislav Strmiska Berta Casar Piero Crespo Vivian de los Rios J. Ignacio Casal Yazan Haddad Roman Guran Tomas Eckschlager Petra Pokorna Zbynek Heger Vojtech Adam
author_facet	Miguel Angel Merlos Rodrigo Hana Michalkova Vladislav Strmiska Berta Casar Piero Crespo Vivian de los Rios J. Ignacio Casal Yazan Haddad Roman Guran Tomas Eckschlager Petra Pokorna Zbynek Heger Vojtech Adam
author_sort	Miguel Angel Merlos Rodrigo
title	Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma
title_short	Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma
title_full	Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma
title_fullStr	Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma
title_full_unstemmed	Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma
title_sort	metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c380e720965d4d49b73aadef566e6723
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Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma

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