Cancer-associated fibroblasts modify lung cancer metabolism involving ROS and TGF-β signaling
Autor: | Aránzazu García-Grande, María José Coronado, Clara Salas, Sara Laine-Menéndez, José Miguel García, Raquel Laza-Briviesca, Ramiro J. Vicente-Blanco, Paloma Martín-Acosta, Fernando Franco, Alberto Cruz-Bermúdez, Atocha Romero, Mariano Provencio, Juan Cristobal Sanchez, Cristina Alfaro, Virginia Calvo |
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Přispěvatelé: | UAM. Departamento de Anatomía Patológica, UAM. Departamento de Medicina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Lung Neoplasms Medicina Adenocarcinoma of Lung Biochemistry Cancer associated fibroblasts mitochondria 03 medical and health sciences 0302 clinical medicine Cancer-Associated Fibroblasts Transforming Growth Factor beta Fibrosis Physiology (medical) Tumor Microenvironment Humans Medicine Reverse Warburg effect Lung cancer Fibroblast Lung Cancer Neoplasm Staging Tumor microenvironment business.industry Cellular Reprogramming medicine.disease OXPHOS Coculture Techniques Metabolism 030104 developmental biology medicine.anatomical_structure A549 Cells Cell culture Cancer research Reactive Oxygen Species business Glycolysis 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Biblos-e Archivo. Repositorio Institucional de la UAM instname |
ISSN: | 0891-5849 |
Popis: | 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. 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. |
Databáze: | OpenAIRE |
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