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MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment

To overcome the lack of effective pharmacological treatments for high-risk neuroblastoma (HR-NB), the development of novel in vitro and in vivo models that better recapitulate the disease is required. Here, we used an in vitro multiclonal cell model encompassing NB cell differentiation stages, to id...

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Autores principales: Garbati, Patrizia, Barbieri, Raffaella, Cangelosi, Davide, Zanon, Carlo, Costa, Delfina, Eva, Alessandra, Thellung, Stefano, Calderoni, Matilde, Baldini, Francesca, Tonini, Gian Paolo, Modesto, Paola, Florio, Tullio, Pagano, Aldo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692293/
https://www.ncbi.nlm.nih.gov/pubmed/33153038
http://dx.doi.org/10.3390/biomedicines8110471
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author Garbati, Patrizia
Barbieri, Raffaella
Cangelosi, Davide
Zanon, Carlo
Costa, Delfina
Eva, Alessandra
Thellung, Stefano
Calderoni, Matilde
Baldini, Francesca
Tonini, Gian Paolo
Modesto, Paola
Florio, Tullio
Pagano, Aldo
author_facet Garbati, Patrizia
Barbieri, Raffaella
Cangelosi, Davide
Zanon, Carlo
Costa, Delfina
Eva, Alessandra
Thellung, Stefano
Calderoni, Matilde
Baldini, Francesca
Tonini, Gian Paolo
Modesto, Paola
Florio, Tullio
Pagano, Aldo
author_sort Garbati, Patrizia
collection PubMed
description To overcome the lack of effective pharmacological treatments for high-risk neuroblastoma (HR-NB), the development of novel in vitro and in vivo models that better recapitulate the disease is required. Here, we used an in vitro multiclonal cell model encompassing NB cell differentiation stages, to identify potential novel pharmacological targets. This model allowed us to identify, by low-density RT-PCR arrays, two gene sets, one over-expressed during NB cell differentiation, and the other up-regulated in more malignant cells. Challenging two HR-NB gene expression datasets, we found that these two gene sets are related to high and low survival, respectively. Using mouse NB cisplatin-treated xenografts, we identified two genes within the list associated to the malignant stage (MCM2 and carbonic anhydrase 9), whose expression is positively correlated with tumor growth. Thus, we tested their pharmacological targeting as potential therapeutic strategy. We measured mice survival and tumor growth rate after xenografts of human NB treated with cisplatin in the presence of MCM2/carbonic anhydrase 9 inhibitors (ciprofloxacin and acetazolamide). MCM2 or carbonic anhydrase 9 inhibition significantly increased cisplatin activity, supporting their possible testing for NB therapy.
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spelling pubmed-76922932020-11-28 MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment Garbati, Patrizia Barbieri, Raffaella Cangelosi, Davide Zanon, Carlo Costa, Delfina Eva, Alessandra Thellung, Stefano Calderoni, Matilde Baldini, Francesca Tonini, Gian Paolo Modesto, Paola Florio, Tullio Pagano, Aldo Biomedicines Article To overcome the lack of effective pharmacological treatments for high-risk neuroblastoma (HR-NB), the development of novel in vitro and in vivo models that better recapitulate the disease is required. Here, we used an in vitro multiclonal cell model encompassing NB cell differentiation stages, to identify potential novel pharmacological targets. This model allowed us to identify, by low-density RT-PCR arrays, two gene sets, one over-expressed during NB cell differentiation, and the other up-regulated in more malignant cells. Challenging two HR-NB gene expression datasets, we found that these two gene sets are related to high and low survival, respectively. Using mouse NB cisplatin-treated xenografts, we identified two genes within the list associated to the malignant stage (MCM2 and carbonic anhydrase 9), whose expression is positively correlated with tumor growth. Thus, we tested their pharmacological targeting as potential therapeutic strategy. We measured mice survival and tumor growth rate after xenografts of human NB treated with cisplatin in the presence of MCM2/carbonic anhydrase 9 inhibitors (ciprofloxacin and acetazolamide). MCM2 or carbonic anhydrase 9 inhibition significantly increased cisplatin activity, supporting their possible testing for NB therapy. MDPI 2020-11-03 /pmc/articles/PMC7692293/ /pubmed/33153038 http://dx.doi.org/10.3390/biomedicines8110471 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Garbati, Patrizia
Barbieri, Raffaella
Cangelosi, Davide
Zanon, Carlo
Costa, Delfina
Eva, Alessandra
Thellung, Stefano
Calderoni, Matilde
Baldini, Francesca
Tonini, Gian Paolo
Modesto, Paola
Florio, Tullio
Pagano, Aldo
MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment
title MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment
title_full MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment
title_fullStr MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment
title_full_unstemmed MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment
title_short MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment
title_sort mcm2 and carbonic anhydrase 9 are novel potential targets for neuroblastoma pharmacological treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692293/
https://www.ncbi.nlm.nih.gov/pubmed/33153038
http://dx.doi.org/10.3390/biomedicines8110471
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