Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients

Wilms tumour (WT) is the most common renal tumour in children. Most WT patients respond to chemotherapy, but subsets of tumours develop resistance to chemotherapeutic agents, which is a major obstacle in their successful treatment. Multidrug resistance transporters play a crucial role in the develop...

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Autores: Hontecillas Prieto, Lourdes, García-Domínguez, Daniel J., Pascual Vaca, Diego, García Mejías, Rosa, Marcilla, David, Ramírez Villar, Gema, Álava Casado, Enrique de
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/96823
Acceso en línea:https://hdl.handle.net/11441/96823
https://doi.org/108632/oncotarget 14491
Access Level:acceso abierto
Palabra clave:Wilms tumours
Multidrug resistance transporters
MDR3
MRP1
Blastemal stratification
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spelling Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patientsHontecillas Prieto, LourdesGarcía-Domínguez, Daniel J.Pascual Vaca, DiegoGarcía Mejías, RosaMarcilla, DavidRamírez Villar, GemaÁlava Casado, Enrique deWilms tumoursMultidrug resistance transportersMDR3MRP1Blastemal stratificationWilms tumour (WT) is the most common renal tumour in children. Most WT patients respond to chemotherapy, but subsets of tumours develop resistance to chemotherapeutic agents, which is a major obstacle in their successful treatment. Multidrug resistance transporters play a crucial role in the development of resistance in cancer due to the efflux of anticancer agents out of cells. The aim of this study was to explore several human multidrug resistance transporters in 46 WT and 40 nonneoplastic control tissues (normal kidney) from patients selected after chemotherapy treatment SIOP 93–01, SIOP 2001. Our data showed that the majority of the studied multidrug resistance transporters were downregulated or unchanged between tumours and control tissues. However, BCRP1, MDR3 and MRP1 were upregulated in tumours versus control tissues. MDR3 and MRP1 overexpression correlated with highrisk tumours (SIOP classification) (p = 0.0022 and p < 0.0001, respectively) and the time of disease-free survival was significantly shorter in patients with high transcript levels of MDR3 (p = 0.0359). MDR3 and MRP1 play a role in drug resistance in WT treatment, probably by alteration of an unspecific drug excretion system. Besides, within the blastemal subtype, we observed patients with low MDR3 expression were significantly associated with a better outcome than patients with high MDR3 expression. We could define two types of blastemal WT associated with different disease outcomes, enabling the stratification of blastemal WT patients based on the expression levels of the multidrug resistance transporter MDR3.Ministerio de Economía y Competitividad PI1401466, RD06/0020/0059, PI1100018, CD06/00001Red Tematica de Investigacion Cooperativa en Cancer RD12/0036/0017Unión Europea FP7-HEALTH- 2011-two-stage, Project ID 278742 EUROSARCInstituto de Salud Carlos III FIS PI13/02282Impact JournalsInstituto de Biomedicina de Sevilla (IBIS)2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/96823https://doi.org/108632/oncotarget 14491reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésOncotarget, 8 (7), 1-14.info:eu-repo/semantics/openAccessoai:idus.us.es:11441/968232026-06-17T12:51:07Z
dc.title.none.fl_str_mv Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients
title Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients
spellingShingle Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients
Hontecillas Prieto, Lourdes
Wilms tumours
Multidrug resistance transporters
MDR3
MRP1
Blastemal stratification
title_short Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients
title_full Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients
title_fullStr Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients
title_full_unstemmed Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients
title_sort Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients
dc.creator.none.fl_str_mv Hontecillas Prieto, Lourdes
García-Domínguez, Daniel J.
Pascual Vaca, Diego
García Mejías, Rosa
Marcilla, David
Ramírez Villar, Gema
Álava Casado, Enrique de
author Hontecillas Prieto, Lourdes
author_facet Hontecillas Prieto, Lourdes
García-Domínguez, Daniel J.
Pascual Vaca, Diego
García Mejías, Rosa
Marcilla, David
Ramírez Villar, Gema
Álava Casado, Enrique de
author_role author
author2 García-Domínguez, Daniel J.
Pascual Vaca, Diego
García Mejías, Rosa
Marcilla, David
Ramírez Villar, Gema
Álava Casado, Enrique de
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Biomedicina de Sevilla (IBIS)
dc.subject.none.fl_str_mv Wilms tumours
Multidrug resistance transporters
MDR3
MRP1
Blastemal stratification
topic Wilms tumours
Multidrug resistance transporters
MDR3
MRP1
Blastemal stratification
description Wilms tumour (WT) is the most common renal tumour in children. Most WT patients respond to chemotherapy, but subsets of tumours develop resistance to chemotherapeutic agents, which is a major obstacle in their successful treatment. Multidrug resistance transporters play a crucial role in the development of resistance in cancer due to the efflux of anticancer agents out of cells. The aim of this study was to explore several human multidrug resistance transporters in 46 WT and 40 nonneoplastic control tissues (normal kidney) from patients selected after chemotherapy treatment SIOP 93–01, SIOP 2001. Our data showed that the majority of the studied multidrug resistance transporters were downregulated or unchanged between tumours and control tissues. However, BCRP1, MDR3 and MRP1 were upregulated in tumours versus control tissues. MDR3 and MRP1 overexpression correlated with highrisk tumours (SIOP classification) (p = 0.0022 and p < 0.0001, respectively) and the time of disease-free survival was significantly shorter in patients with high transcript levels of MDR3 (p = 0.0359). MDR3 and MRP1 play a role in drug resistance in WT treatment, probably by alteration of an unspecific drug excretion system. Besides, within the blastemal subtype, we observed patients with low MDR3 expression were significantly associated with a better outcome than patients with high MDR3 expression. We could define two types of blastemal WT associated with different disease outcomes, enabling the stratification of blastemal WT patients based on the expression levels of the multidrug resistance transporter MDR3.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/96823
https://doi.org/108632/oncotarget 14491
url https://hdl.handle.net/11441/96823
https://doi.org/108632/oncotarget 14491
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Oncotarget, 8 (7), 1-14.
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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