Smoking-Induced CXCL14 Expression in the Human Airway Epithelium Links Chronic Obstructive Pulmonary Disease to Lung Cancer

被引:36
|
作者
Shaykhiev, Renat [1 ]
Sackrowitz, Rachel [2 ]
Fukui, Tomoya [1 ]
Zuo, Wu-Lin [1 ]
Chao, Ion Wa [1 ]
Strulovici-Barel, Yael [1 ]
Downey, Robert J. [3 ]
Crystal, Ronald G. [1 ,2 ]
机构
[1] Weill Cornell Med Coll, Dept Med Genet, New York, NY 10065 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Med, Div Pulm & Crit Care Med, New York, NY 10021 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Surg, Thorac Serv, New York, NY 10021 USA
基金
美国国家卫生研究院;
关键词
CXCL14; airway epithelium; smoking; COPD; lung cancer; IN-VIVO; CHEMOKINE BRAK; GROWTH-FACTOR; CELL; BREAST; DIFFERENTIATION; LOCALIZATION; INFLAMMATION; BRAK/CXCL14; SUGGESTS;
D O I
10.1165/rcmb.2012-0396OC
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 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.
引用
收藏
页码:418 / 425
页数:8
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