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JCI Insight. 2016 Nov 17;1(19):e88814.

The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer.

Author information

1
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center.
2
Department of Biochemistry.
3
Department of Biostatistics, and.
4
Department of Chemical and Biomolecular Engineering, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
5
Pulmonary Center and Section of Computational Biomedicine, Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
6
Departments of Pathology, Microbiology, and Immunology.
7
Department of Chemical and Biomolecular Engineering, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Molecular Physiology and Biophysics, and.
8
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center,; Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.

Abstract

The molecular determinants of lung cancer risk remain largely unknown. Airway epithelial cells are prone to assault by risk factors and are considered to be the primary cell type involved in the field of cancerization. To investigate risk-associated changes in the bronchial epithelium proteome that may offer new insights into the molecular pathogenesis of lung cancer, proteins were identified in the airway epithelial cells of bronchial brushing specimens from risk-stratified individuals by shotgun proteomics. Differential expression of selected proteins was validated by parallel reaction monitoring mass spectrometry in an independent set of individual bronchial brushings. We identified 2,869 proteins, of which 312 proteins demonstrated a trend in expression. Pathway analysis revealed enrichment of carbohydrate metabolic enzymes in high-risk individuals. Glucose consumption and lactate production were increased in human bronchial epithelial BEAS2B cells treated with cigarette smoke condensate for 7 months. Increased lipid biosynthetic capacity and net reductive carboxylation were revealed by metabolic flux analyses of [U-13C5] glutamine in this in vitro model, suggesting profound metabolic reprogramming in the airway epithelium of high-risk individuals. These results provide a rationale for the development of potentially new chemopreventive strategies and selection of patients for surveillance programs.

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