Publication detail

Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma

MERLOS RODRIGO, M. MICHÁLKOVÁ, H. STRMISKA, V. CASAR, B. CRESPO, P. DE LOS RIOS, V. CASAL ÁLVAREZ, J. HADDAD, Y. GURÁŇ, R. ECKSCHLAGER, T. POKORNÁ, P. HEGER, Z. ADAM, V.

Original Title

Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma

Type

journal article in Web of Science

Language

English

Original 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.

Keywords

Metallothionein-3; cancer; neuroblastoma; cisplatin; chemoresistance

Authors

MERLOS RODRIGO, M.; MICHÁLKOVÁ, H.; STRMISKA, V.; CASAR, B.; CRESPO, P.; DE LOS RIOS, V.; CASAL ÁLVAREZ, J.; HADDAD, Y.; GURÁŇ, R.; ECKSCHLAGER, T.; POKORNÁ, P.; HEGER, Z.; ADAM, V.

Released

9. 3. 2021

Publisher

Springer Nature

ISBN

2045-2322

Periodical

Scientific Reports

Year of study

11

Number

1

State

United Kingdom of Great Britain and Northern Ireland

Pages from

1

Pages to

14

Pages count

14

URL

https://www.nature.com/articles/s41598-021-84185-x

Full text in the Digital Library

http://hdl.handle.net/11012/196716

BibTex

@article{BUT171008,
  author="Miguel Ángel {Merlos Rodrigo} and Hana {Michálková} and Vladislav {Strmiska} and Berta {Casar} and Piero {Crespo} and Vivian {De los Rios} and José Ignacio {Casal Álvarez} and Yazan Abdulmajeed Eyadh {Haddad} and Roman {Guráň} and Tomáš {Eckschlager} and Petra {Pokorná} and Zbyněk {Heger} and Vojtěch {Adam}",
  title="Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma",
  journal="Scientific Reports",
  year="2021",
  volume="11",
  number="1",
  pages="1--14",
  doi="10.1038/s41598-021-84185-x",
  issn="2045-2322",
  url="https://www.nature.com/articles/s41598-021-84185-x"
}