Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targets

Detalhes bibliográficos
Autor(a) principal: Gonçalves, Vera M.
Data de Publicação: 2013
Outros Autores: Honavar, Mrinalini, Pinheiro, Céline, Martinho, Olga, Pires, Manuel Melo, Pinheiro, Célia, Cordeiro, Michelle, Bebiano, Gil, Costa, Paulo, Palmeirim, I., Reis, R. M., Baltazar, Fátima
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/24171
Resumo: Background. Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD147 and to assess the therapeutic impact of MCT inhibition in gliomas. Methods. MCTs and CD147 expressions were characterized by immunohistochemistry in nonneoplastic brain and glioma samples. The effect of CHC (MCT inhibitor) and MCT1 silencing was assessed in in vitro and in vivo glioblastoma models. Results. MCT1, MCT4, and CD147 were overexpressed in the plasma membrane of glioblastomas, compared with diffuse astrocytomas and nonneoplastic brain. CHC decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT membrane expression. MCT1 downregulation showed similar effects on different glioma cells, supporting CHC as an MCT1 inhibitor. There was a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed. Conclusions. This is the most comprehensive study reporting the expression of MCTs and CD147 in gliomas. The MCT1 inhibitor CHC exhibited anti-tumoral and anti-angiogenic activity in gliomas and, of importance, enhanced the effect of temozolomide. Thus, our results suggest that development of therapeutic approaches targeting MCT1 may be a promising strategy in glioblastoma treatment.
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spelling Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targetsCD147CHCGlioblastomasGliomasGlycolytic metabolismLactateMonocarboxylate transportersScience & TechnologyBackground. Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD147 and to assess the therapeutic impact of MCT inhibition in gliomas. Methods. MCTs and CD147 expressions were characterized by immunohistochemistry in nonneoplastic brain and glioma samples. The effect of CHC (MCT inhibitor) and MCT1 silencing was assessed in in vitro and in vivo glioblastoma models. Results. MCT1, MCT4, and CD147 were overexpressed in the plasma membrane of glioblastomas, compared with diffuse astrocytomas and nonneoplastic brain. CHC decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT membrane expression. MCT1 downregulation showed similar effects on different glioma cells, supporting CHC as an MCT1 inhibitor. There was a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed. Conclusions. This is the most comprehensive study reporting the expression of MCTs and CD147 in gliomas. The MCT1 inhibitor CHC exhibited anti-tumoral and anti-angiogenic activity in gliomas and, of importance, enhanced the effect of temozolomide. Thus, our results suggest that development of therapeutic approaches targeting MCT1 may be a promising strategy in glioblastoma treatment.This work was supported by the Life and Health Sciences Research Institute, University of Minho, Portugal, and Fundação para a Ciência e Tecnologia 845 (SFRH/BI/33503/2008 to V.M.G., SFRH/BPD/ 69479/2010 to C.P., and SFRH/BD/36463/2007 to O.M.).Oxford University PressUniversidade do MinhoGonçalves, Vera M.Honavar, MrinaliniPinheiro, CélineMartinho, OlgaPires, Manuel MeloPinheiro, CéliaCordeiro, MichelleBebiano, GilCosta, PauloPalmeirim, I.Reis, R. M.Baltazar, Fátima2013-022013-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/24171eng1522-851710.1093/neuonc/nos29823258846http://neuro-oncology.oxfordjournals.org/content/15/2/172.full.pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:19:15Zoai:repositorium.sdum.uminho.pt:1822/24171Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:12:09.989789Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targets
title Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targets
spellingShingle Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targets
Gonçalves, Vera M.
CD147
CHC
Glioblastomas
Gliomas
Glycolytic metabolism
Lactate
Monocarboxylate transporters
Science & Technology
title_short Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targets
title_full Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targets
title_fullStr Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targets
title_full_unstemmed Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targets
title_sort Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as therapeutic targets
author Gonçalves, Vera M.
author_facet Gonçalves, Vera M.
Honavar, Mrinalini
Pinheiro, Céline
Martinho, Olga
Pires, Manuel Melo
Pinheiro, Célia
Cordeiro, Michelle
Bebiano, Gil
Costa, Paulo
Palmeirim, I.
Reis, R. M.
Baltazar, Fátima
author_role author
author2 Honavar, Mrinalini
Pinheiro, Céline
Martinho, Olga
Pires, Manuel Melo
Pinheiro, Célia
Cordeiro, Michelle
Bebiano, Gil
Costa, Paulo
Palmeirim, I.
Reis, R. M.
Baltazar, Fátima
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Gonçalves, Vera M.
Honavar, Mrinalini
Pinheiro, Céline
Martinho, Olga
Pires, Manuel Melo
Pinheiro, Célia
Cordeiro, Michelle
Bebiano, Gil
Costa, Paulo
Palmeirim, I.
Reis, R. M.
Baltazar, Fátima
dc.subject.por.fl_str_mv CD147
CHC
Glioblastomas
Gliomas
Glycolytic metabolism
Lactate
Monocarboxylate transporters
Science & Technology
topic CD147
CHC
Glioblastomas
Gliomas
Glycolytic metabolism
Lactate
Monocarboxylate transporters
Science & Technology
description Background. Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD147 and to assess the therapeutic impact of MCT inhibition in gliomas. Methods. MCTs and CD147 expressions were characterized by immunohistochemistry in nonneoplastic brain and glioma samples. The effect of CHC (MCT inhibitor) and MCT1 silencing was assessed in in vitro and in vivo glioblastoma models. Results. MCT1, MCT4, and CD147 were overexpressed in the plasma membrane of glioblastomas, compared with diffuse astrocytomas and nonneoplastic brain. CHC decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT membrane expression. MCT1 downregulation showed similar effects on different glioma cells, supporting CHC as an MCT1 inhibitor. There was a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed. Conclusions. This is the most comprehensive study reporting the expression of MCTs and CD147 in gliomas. The MCT1 inhibitor CHC exhibited anti-tumoral and anti-angiogenic activity in gliomas and, of importance, enhanced the effect of temozolomide. Thus, our results suggest that development of therapeutic approaches targeting MCT1 may be a promising strategy in glioblastoma treatment.
publishDate 2013
dc.date.none.fl_str_mv 2013-02
2013-02-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/24171
url http://hdl.handle.net/1822/24171
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1522-8517
10.1093/neuonc/nos298
23258846
http://neuro-oncology.oxfordjournals.org/content/15/2/172.full.pdf
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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