Smoking-induced CXCL14 expression in the human airway epithelium links chronic obstructive pulmonary disease to lung cancer Journal Article


Authors: Shaykhiev, R.; Sackrowitz, R.; Fukui, T.; Zuo, W. L.; Chao, I. W.; Strulovici-Barel, Y.; Downey, R. J.; Crystal, R. G.
Article Title: Smoking-induced CXCL14 expression in the human airway epithelium links chronic obstructive pulmonary disease to lung cancer
Abstract: CXCL14, a recently described epithelial cytokine, plays putative multiple roles in inflammation and carcinogenesis. In the context that chronic obstructive pulmonary disease (COPD) and lung cancer are both smoking-related disorders associated with airway epithelial disorder and inflammation, we hypothesized that the airway epithelium responds to cigarette smoking with altered CXCL14 gene expression, contributing to the disease-relevant phenotype. Using genome-wide microarrays with subsequent immunohistochemical analysis, the data demonstrate that the expression of CXCL14 is up-regulated in the airway epithelium of healthy smokers and further increased in COPD smokers, especially within hyperplastic/metaplastic lesions, in association with multiple genes relevant to epithelial structural integrity and cancer. In vitro experiments revealed that the expression of CXCL14 is induced in the differentiated airway epithelium by cigarette smoke extract, and that epidermal growth factor mediates CXCL14 upregulation in the airway epithelium through its effects on the basal stem/progenitor cell population. Analyses of two independent lung cancer cohorts revealed a dramatic up-regulation of CXCL14 expression in adenocarcinoma and squamous-cell carcinoma. High expression of the COPD-associated CXCL14-correlating cluster of geneswas linked in lung adenocarcinoma with poor survival. These data suggest that the smoking-induced expression of CXCL14 in the airway epithelium represents a novel potential molecular link between smoking-associated airway epithelial injury, COPD, and lung cancer. Copyright © 2013 by the American Thoracic Society.
Keywords: immunohistochemistry; adult; cancer survival; clinical article; controlled study; human tissue; protein expression; middle aged; survival analysis; human cell; carcinoma, squamous cell; adenocarcinoma; phenotype; cells, cultured; gene expression; lung neoplasms; epidermal growth factor receptor; genome-wide association study; lung cancer; smoking; stem cell; lung adenocarcinoma; microarray analysis; epithelial cells; stem cells; upregulation; lung squamous cell carcinoma; corticosteroid; transcriptome; respiratory mucosa; chronic obstructive lung disease; pulmonary disease, chronic obstructive; respiratory epithelium; beta adrenergic receptor stimulating agent; copd; respiratory system; cholinergic receptor blocking agent; chemokines, cxc; complex mixtures; airway epithelium; cxcl14; cxcl14 chemokine
Journal Title: American Journal of Respiratory Cell and Molecular Biology
Volume: 49
Issue: 3
ISSN: 1044-1549
Publisher: American Thoracic Society  
Date Published: 2013-09-01
Start Page: 418
End Page: 425
Language: English
DOI: 10.1165/rcmb.2012-0396OC
PROVIDER: scopus
PUBMED: 23597004
PMCID: PMC3824052
DOI/URL:
Notes: --- - "Export Date: 1 October 2013" - "CODEN: AJRBE" - "Source: Scopus"
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Robert J Downey
    254 Downey