Smoking-induced CXCL14 expression in the human airway epithelium links chronic obstructive pulmonary disease to lung cancer. Academic Article uri icon

Overview

MeSH

  • Adult
  • Cells, Cultured
  • Epithelial Cells
  • Female
  • Gene Expression
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Respiratory Mucosa
  • Respiratory System
  • Stem Cells
  • Survival Analysis

MeSH Major

  • Adenocarcinoma
  • Carcinoma, Squamous Cell
  • Chemokines, CXC
  • Complex Mixtures
  • Lung Neoplasms
  • Pulmonary Disease, Chronic Obstructive
  • Smoking

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 up-regulation 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 genes was 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.

publication date

  • September 2013

has subject area

  • Adenocarcinoma
  • Adult
  • Carcinoma, Squamous Cell
  • Cells, Cultured
  • Chemokines, CXC
  • Complex Mixtures
  • Epithelial Cells
  • Female
  • Gene Expression
  • Genome-Wide Association Study
  • Humans
  • Lung Neoplasms
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive
  • Respiratory Mucosa
  • Respiratory System
  • Smoking
  • Stem Cells
  • Survival Analysis

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3824052

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2012-0396OC

PubMed ID

  • 23597004

Additional Document Info

start page

  • 418

end page

  • 425

volume

  • 49

number

  • 3