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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doaj-c380e720965d4d49b73aadef566e67232021-03-11T12:21:50ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111410.1038/s41598-021-84185-xMetallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastomaMiguel Angel Merlos Rodrigo0Hana Michalkova1Vladislav Strmiska2Berta Casar3Piero Crespo4Vivian de los Rios5J. Ignacio Casal6Yazan Haddad7Roman Guran8Tomas Eckschlager9Petra Pokorna10Zbynek Heger11Vojtech Adam12Department of Chemistry and Faculty of AgriSciences, Mendel University in BrnoDepartment of Chemistry and Faculty of AgriSciences, Mendel University in BrnoDepartment of Chemistry and Faculty of AgriSciences, Mendel University in BrnoInstituto de Biomedicina Y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas (CSIC), Universidad de CantabriaInstituto de Biomedicina Y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas (CSIC), Universidad de CantabriaFunctional Proteomics, Department of Cellular and Molecular Medicine and Proteomic Facility, Centro de Investigaciones Biológicas (CIB-CSIC)Functional Proteomics, Department of Cellular and Molecular Medicine and Proteomic Facility, Centro de Investigaciones Biológicas (CIB-CSIC)Department of Chemistry and Faculty of AgriSciences, Mendel University in BrnoDepartment of Chemistry and Faculty of AgriSciences, Mendel University in BrnoDepartment of Paediatric Haematology and Oncology, Charles University and University Hospital MotolDepartment of Oncology, Charles University and University Hospital MotolDepartment of Chemistry and Faculty of AgriSciences, Mendel University in BrnoDepartment of Chemistry and Faculty of AgriSciences, Mendel University in BrnoAbstract 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.https://doi.org/10.1038/s41598-021-84185-x |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-84185-x |
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