Clinical significance of metabolism-related biomarkers in non-Hodgkin lymphoma-MCT1 as potential target in diffuse large B cell lymphoma

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorAFONSO, Julieta
dc.contributor.authorPINTO, Tatiana
dc.contributor.authorSIMOES-SOUSA, Susana
dc.contributor.authorSCHMITT, Fernando
dc.contributor.authorLONGATTO-FILHO, Adhemar
dc.contributor.authorPINHEIRO, Celine
dc.contributor.authorMARQUES, Herlander
dc.contributor.authorBALTAZAR, Fatima
dc.date.accessioned2019-06-26T17:33:49Z
dc.date.available2019-06-26T17:33:49Z
dc.date.issued2019
dc.description.abstractPurposeIncreased glycolytic activity with accumulation of extracellular lactate is regarded as a hallmark of cancer. In lymphomas, FDG-PET has undeniable diagnostic and prognostic value, corroborating that these tumours are avid for glucose. However, the role of glycolytic metabolism-related molecules in lymphoma is not well known. Here, we aimed to evaluate the clinical and prognostic significance of a panel of glycolytic metabolism-related molecules in primary non-Hodgkin lymphomas (NHL) and to test in vitro the putative therapeutic impact of lactate transport inhibition.MethodsWe assessed, by immunohistochemistry, the expression of the metabolism-related molecules MCT1, MCT2, MCT4, CD147, GLUT1, LDHA and CAIX in both tumour and stroma compartments of tissue sections obtained from 104 NHL patients. In addition, the lymphoma-derived cell lines OZ and DOHH-2 were used to evaluate the effect of AZD3965 on their viability and on apoptosis induction, as well as on extracellular lactate accumulation.ResultsWe found that expression of MCT1 in the NHL tumour compartment was significantly associated with a poor clinicopathological profile. We also found that MCT4 and CAIX were present in the stromal compartment and correlated with an aggressive phenotype, while MCT1 was absent in this compartment. In addition, we found that AZD3965-mediated disruption of MCT1 activity led to inhibited NHL cell viability and extracellular lactate accumulation, while increasing apoptotic cell death.ConclusionsOur results indicate that elevated glycolytic activity is associated with NHL aggressiveness, pointing at metabolic cooperation, mediated by MCT1 and MCT4, between tumour cells and their surrounding stroma. MCT1 may serve as a target to treat NHL (diffuse large B cell lymphoma) patients with high MCT1/low MCT4 expressing tumours. Further (pre-)clinical studies are required to allow the design of novel therapeutic strategies aimed at e.g. reprogramming the tumour microenvironment.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipNorthern Portugal Regional Operational Programme (NORTE 2020) through the European Regional Development Fund (FEDER) [NORTE-01-0145-FEDER-000013]
dc.description.sponsorshipNorthern Portugal Regional Operational Programme (NORTE 2020) through Competitiveness Factors Operational Programme (COMPETE)
dc.description.sponsorshipFoundation for Science and Technology (FCT) [POCI-01-0145-FEDER-007038]
dc.description.sponsorshipFCT [SFRH/BPD/116784/2016]
dc.identifier.citationCELLULAR ONCOLOGY, v.42, n.3, p.303-318, 2019
dc.identifier.doi10.1007/s13402-019-00426-2
dc.identifier.eissn2211-3436
dc.identifier.issn2211-3428
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/32547
dc.language.isoeng
dc.publisherSPRINGEReng
dc.relation.ispartofCellular Oncology
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright SPRINGEReng
dc.subjectNon-Hodgkin lymphomaeng
dc.subjectDiffuse large B cell lymphomaeng
dc.subjectWarburg effecteng
dc.subjectMonocarboxylate transporterseng
dc.subjectMetabolic symbiosiseng
dc.subjectAZD3965eng
dc.subject.othermonocarboxylate transporterseng
dc.subject.otherlactate-dehydrogenaseeng
dc.subject.otherresponse criteriaeng
dc.subject.otherglucose-metabolismeng
dc.subject.otherinhibitor azd3965eng
dc.subject.othercancereng
dc.subject.otherexpressioneng
dc.subject.othergrowtheng
dc.subject.othercd147eng
dc.subject.othermct1eng
dc.subject.wosOncologyeng
dc.subject.wosCell Biologyeng
dc.subject.wosPathologyeng
dc.titleClinical significance of metabolism-related biomarkers in non-Hodgkin lymphoma-MCT1 as potential target in diffuse large B cell lymphomaeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryPortugal
hcfmusp.affiliation.countryInglaterra
hcfmusp.affiliation.countryisopt
hcfmusp.affiliation.countryisogb
hcfmusp.author.externalAFONSO, Julieta:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, P-4710057 Braga, Portugal; PT Govt Associate Lab, ICVS 3Bs, Braga, Portugal
hcfmusp.author.externalPINTO, Tatiana:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, P-4710057 Braga, Portugal; PT Govt Associate Lab, ICVS 3Bs, Braga, Portugal
hcfmusp.author.externalSIMOES-SOUSA, Susana:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, P-4710057 Braga, Portugal; PT Govt Associate Lab, ICVS 3Bs, Braga, Portugal; Inst Canc Res, Div Canc Biol, London, England
hcfmusp.author.externalSCHMITT, Fernando:Univ Porto, Inst Mol Pathol & Immunol IPATIMUP, Porto, Portugal; Univ Porto, Med Fac, Porto, Portugal
hcfmusp.author.externalPINHEIRO, Celine:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, P-4710057 Braga, Portugal; PT Govt Associate Lab, ICVS 3Bs, Braga, Portugal; Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil; Barretos Sch Hlth Sci Dr Paulo Prata FACISB, Sao Paulo, Brazil
hcfmusp.author.externalMARQUES, Herlander:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, P-4710057 Braga, Portugal; PT Govt Associate Lab, ICVS 3Bs, Braga, Portugal; Hosp Braga, Dept Oncol, Braga, Portugal; Univ Porto, Ctr Hlth Technol & Serv Res, CINTESIS, Fac Med, Porto, Portugal
hcfmusp.author.externalBALTAZAR, Fatima:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, P-4710057 Braga, Portugal; PT Govt Associate Lab, ICVS 3Bs, Braga, Portugal
hcfmusp.citation.scopus27
hcfmusp.contributor.author-fmusphcADHEMAR LONGATTO FILHO
hcfmusp.description.beginpage303
hcfmusp.description.endpage318
hcfmusp.description.issue3
hcfmusp.description.volume42
hcfmusp.origemWOS
hcfmusp.origem.pubmed30790227
hcfmusp.origem.scopus2-s2.0-85062011171
hcfmusp.origem.wosWOS:000469354700005
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hcfmusp.publisher.countryNETHERLANDSeng
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