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

2013-02Journal article Open access
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dc.contributor.authorMiranda-Goncalves, Vera
dc.contributor.authorHonavar, Mrinalini
dc.contributor.authorPinheiro, Celine
dc.contributor.authorMartinho, Olga
dc.contributor.authorPires, Manuel M.
dc.contributor.authorPinheiro, Celia
dc.contributor.authorCordeiro, Michelle
dc.contributor.authorBebiano, Gil
dc.contributor.authorCosta, Paulo
dc.contributor.authorPalmeirim, Isabel
dc.contributor.authorReis, Rui M.
dc.contributor.authorBaltazar, Fatima
dc.date.accessioned2018-12-07T14:52:58Z
dc.date.available2018-12-07T14:52:58Z
dc.date.issued2013-02
dc.description.abstractBackground. 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 CD 147 and to assess the therapeutic impact of MCT inhibition in gliomas. Methods. MCTs and CD 147 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 CD 147 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 CD 147 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.
dc.description.sponsorshipLife and Health Sciences Research Institute, University of Minho, Portugal; Fundacao para a Ciencia e Tecnologia [SFRH/BI/33503/2008, SFRH/BPD/69479/2010, SFRH/BD/36463/2007]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1093/neuonc/nos298
dc.identifier.issn1522-8517
dc.identifier.issn1523-5866
dc.identifier.urihttp://hdl.handle.net/10400.1/11287
dc.language.isoeng
dc.peerreviewedyes
dc.publisherOxford Univ Press Inc
dc.relationEXPLOITATION OF MONOCARBOXYLATE TRANSPORTERS MCTS AS POTENTIAL THERAPEUTIC TARGETS IN BRAIN TUMOURS
dc.relationTARGETING LACTATE TRANSPORT IN CANCER THERAPY: CERVICAL AND BREAST CANCER AS MODELS
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCentral-nervous-system
dc.subjectAscites tumor-cells
dc.subjectMalignant glioma
dc.subjectCervical-carcinoma
dc.subjectLactate transport
dc.subjectCancer-cells
dc.subjectLung-cancer
dc.subjectIn-Vitro
dc.subjectMetabolism
dc.subjectInhibition
dc.titleMonocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleEXPLOITATION OF MONOCARBOXYLATE TRANSPORTERS MCTS AS POTENTIAL THERAPEUTIC TARGETS IN BRAIN TUMOURS
oaire.awardTitleTARGETING LACTATE TRANSPORT IN CANCER THERAPY: CERVICAL AND BREAST CANCER AS MODELS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBI%2F33503%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F69479%2F2010/PT
oaire.citation.endPage188
oaire.citation.issue2
oaire.citation.startPage172
oaire.citation.titleNeuro-Oncology
oaire.citation.volume15
person.familyNamePalmeirim
person.familyNameBaltazar
person.givenNameIsabel
person.givenNameFatima
person.identifier132668
person.identifier.ciencia-id141A-4DE2-6FF3
person.identifier.ciencia-idFE1F-3F98-8FC3
person.identifier.orcid0000-0003-2282-7829
person.identifier.orcid0000-0002-1770-4544
person.identifier.ridA-8720-2010
person.identifier.scopus-author-id6603305227
person.identifier.scopus-author-id16645087200
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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relation.isAuthorOfPublication6473af3b-b74c-419d-9576-8096fc41b923
relation.isAuthorOfPublication.latestForDiscovery19d625d8-5aae-462b-b83a-ad10a155897f
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relation.isProjectOfPublication.latestForDiscoverya7e76432-8db5-4e85-895a-151cc5ca1ecb

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