Cancer-associated fibroblasts modify lung cancer metabolism involving ROS and TGF-β signaling
Autor (es)
Cruz-Bermúdez, Alberto; Laza-Briviesca, Raquel; Vicente-Blanco, Ramiro J.; García-Grande, Aránzazu; Coronado, Maria José; Laine-Menéndez, Sara; Alfaro, Cristina; Sánchez, Juan Cristóbal; Franco, Fernando; Calvo de Juan, Virginia

Entidad
UAM. Departamento de Anatomía Patológica; UAM. Departamento de MedicinaEditor
Elsevier Inc.Fecha de edición
2018-11-01Cita
10.1016/j.freeradbiomed.2018.10.450
Free Radical Biology and Medicine 130 (2019): 163-173
ISSN
0891-5849DOI
10.1016/j.freeradbiomed.2018.10.450Financiado por
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.Proyecto
Gobierno de España. PI13/01806; Gobierno de España. PIE14/0064Versión del editor
https://doi.org/10.1016/j.freeradbiomed.2018.10.450Materias
Cancer; Cancer associated fibroblasts mitochondria; Metabolism; OXPHOS; Reverse Warburg effect; MedicinaDerechos
© 2018 The Authors
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Resumen
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.
Lista de ficheros
Google Scholar:Cruz-Bermúdez, Alberto
-
Laza-Briviesca, Raquel
-
Vicente-Blanco, Ramiro J.
-
García-Grande, Aránzazu
-
Coronado, Maria José
-
Laine-Menéndez, Sara
-
Alfaro, Cristina
-
Sánchez, Juan Cristóbal
-
Franco, Fernando
-
Calvo de Juan, Virginia
-
Romero, Atocha
-
Martín-Acosta, Paloma
-
Salas, Clara
-
García, José Miguel
-
Provencio Pulla, Mariano
Lista de colecciones del ítem
Registros relacionados
Mostrando ítems relacionados por título, autor, creador y materia.
-
Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1α in NSCLC which can be overcome by OXPHOS inhibition
Cruz-Bermúdez, Alberto; Laza-Briviesca, Raquel; Vicente-Blanco, Ramiro J.; García-Grande, Aránzazu; Coronado, Maria José; Laine-Menéndez, Sara; Palacios-Zambrano, Sara; Moreno-Villa, M. Rocío; Martín Ruiz-Valdepeñas, Asunción; Lendinez, Cristina; Romero, Atocha; Franco, Fernando; Calvo de Juan, Virginia; Alfaro, Cristina; Martín Acosta, Paloma; Salas, Clara; Garcia, José Miguel; Provencio Pulla, Mariano
2019-05-14 -
Concordance between circulating tumor cells and clinical status during follow-up in anaplastic lymphoma kinase (ALK) non-small-cell lung cancer patients
Provencio Pulla, Mariano; Pérez-Callejo, David; Torrente, María; Martín, Paloma; Calvo de Juan, Virginia
; Gutiérrez, Lourdes; Franco, Fernando; Coronado, María José; Cruz-Bermúdez, Juan Luis; Martín Ruiz-Valdepeñas, Asunción; Cruz-Bermúdez, Alberto; Sánchez-Beato, Margarita; Romero, Atocha; García-Grande, Aránzazu
2017-07-31 -
Dynamic circulating tumor DNA quantificaton for the individualization of non-small-cell lung cancer patients treatment
Provencio Pulla, Mariano; Torrente, María; Calvo de Juan, Virginia
; Gutiérrez, Lourdes; Pérez-Callejo, David; Pérez-Barrios, Clara; Barquín, Miguel; Royuela Vicente, Ana; Rodríguez-Alfonso, Begoña; Sotelo, Miguel; Cruz-Bermúdez, Juan Luis; Mendez, Miriam; Cruz-Bermúdez, Alberto; Romero, Atocha
2017-08-07