Cancer-associated fibroblasts modify lung cancer metabolism involving ROS and TGF-β signaling

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dc.contributor.author Cruz-Bermúdez, Alberto
dc.contributor.author Laza-Briviesca, Raquel
dc.contributor.author Vicente-Blanco, Ramiro J.
dc.contributor.author García-Grande, Aránzazu
dc.contributor.author Coronado, Maria José
dc.contributor.author Laine-Menéndez, Sara
dc.contributor.author Alfaro, Cristina
dc.contributor.author Sánchez, Juan Cristóbal
dc.contributor.author Franco, Fernando
dc.contributor.author Calvo, Virginia
dc.contributor.author Romero, Atocha
dc.contributor.author Martín-Acosta, Paloma
dc.contributor.author Salas, Clara
dc.contributor.author García, José Miguel
dc.contributor.author Provencio, Mariano
dc.contributor.other UAM. Departamento de Anatomía Patológica es_ES
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.date.accessioned 2019-10-25T11:07:15Z
dc.date.available 2019-10-25T11:07:15Z
dc.date.issued 2018-11-01
dc.identifier.citation Free Radical Biology and Medicine 130 (2019): 163-173 en_US
dc.identifier.issn 0891-5849 es_ES
dc.identifier.uri http://hdl.handle.net/10486/688986
dc.description.abstract Lung cancer is a major public health problem due to its high incidence and mortality rate. The altered metabolism in lung cancer is key for the diagnosis and has implications on both, the prognosis and the response to treatments. Although Cancer-associated fibroblasts (CAFs) are one of the major components of the tumor microenvironment, little is known about their role in lung cancer metabolism. We studied tumor biopsies from a cohort of 12 stage IIIA lung adenocarcinoma patients and saw a positive correlation between the grade of fibrosis and the glycolysis phenotype (Low PGC-1α and High GAPDH/MT-CO1 ratio mRNA levels). These results were confirmed and extended to other metabolism-related genes through the in silico data analysis from 73 stage IIIA lung adenocarcinoma patients available in TCGA. Interestingly, these relationships are not observed with the CAFs marker α-SMA in both cohorts. To characterize the mechanism, in vitro co-culture studies were carried out using two NSCLC cell lines (A549 and H1299 cells) and two different fibroblast cell lines. Our results confirm that a metabolic reprogramming involving ROS and TGF-β signaling occurs in lung cancer cells and fibroblasts independently of α-SMA induction. Under co-culture conditions, Cancer-Associated fibroblasts increase their glycolytic ability. On the other hand, tumor cells increase their mitochondrial function. Moreover, the differential capability among tumor cells to induce this metabolic shift and also the role of the basal fibroblasts Oxphos Phosphorylation (OXPHOS) function modifying this phenomenon could have implications on both, the diagnosis and prognosis of patients. Further knowledge in the mechanism involved may allow the development of new therapies. en_US
dc.description.sponsorship Work in the authors’ laboratories is supported by ‘‘Instituto de Salud Carlos III’’ PI13/01806 and PIE14/0064 to M.P. A.C-B, received a Spanish Lung Cancer Group fellowship. R.L-B, is supported by Comunidad Autónoma de Madrid “Garantía juvenil” contract. en_US
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Elsevier Inc. en_US
dc.relation.ispartof Free Radical Biology and Medicine en_US
dc.rights © 2018 The Authors en_US
dc.subject.other Cancer en_US
dc.subject.other Cancer associated fibroblasts mitochondria en_US
dc.subject.other Metabolism en_US
dc.subject.other OXPHOS en_US
dc.subject.other Reverse Warburg effect en_US
dc.title Cancer-associated fibroblasts modify lung cancer metabolism involving ROS and TGF-β signaling en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion https://doi.org/10.1016/j.freeradbiomed.2018.10.450 es_ES
dc.identifier.doi 10.1016/j.freeradbiomed.2018.10.450 es_ES
dc.identifier.publicationfirstpage 163 es_ES
dc.identifier.publicationissue 130 es_ES
dc.identifier.publicationlastpage 173 es_ES
dc.relation.projectID Gobierno de España. PI13/01806 es_ES
dc.relation.projectID Gobierno de España. PIE14/0064 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento – NoComercial – SinObraDerivada es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Salas Antón, Clara María (261172)
dc.authorUAM Provencio Pulla, Mariano (262376)


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