Regulatory mechanisms of betacellulin in CXCL8 production from lung cancer cells

Journal of Translational Medicine

Chengshui Chen¹  Xiangdong Wang²  Qun Wang³  Sanda Maria Cretoiu⁴  Beibei Wang¹  Lingyan Wang⁵  Lin Shi¹ 

[1] Department of Pulmonary Medicine, The First affiliated Hospital, Wenzhou Medical University, Wenzhou, China;Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China;Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China;Division of Cellular and Molecular Medicine, Department of Morphological Sciences, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China

关键词: PI3K;    EGFR;    Interleukin-8;    Betacellulin;    Lung cancer;   

Others  :  817643
DOI  :  10.1186/1479-5876-12-70

 received in 2014-01-17, accepted in 2014-03-11,  发布年份 2014

【 摘 要 】

Background

Betacellulin (BTC), a member of the epidermal growth factor (EGF) family, binds and activates ErbB1 and ErbB4 homodimers. BTC was expressed in tumors and involved in tumor growth progression. CXCL8 (interleukin-8) was involved in tumor cell proliferation via the transactivation of the epidermal growth factor receptor (EGFR).

Materials and methods

The present study was designed to investigate the possible interrelation between BTC and CXCL8 in human lung cancer cells (A549) and demonstrated the mechanisms of intracellular signals in the regulation of both functions. Bio-behaviors of A549 were assessed using Cell-IQ Alive Image Monitoring System.

Results

We found that BTC significantly increased the production of CXCL8 through the activation of the EGFR-PI3K/Akt-Erk signal pathway. BTC induced the resistance of human lung cancer cells to TNF-α/CHX-induced apoptosis. Treatments with PI3K inhibitors, Erk1/2 inhibitor, or Erlotinib significantly inhibited BTC-induced CXCL8 production and cell proliferation and movement.

Conclusion

Our data indicated that CXCL8 production from lung cancer cells could be initiated by an autocrine mechanism or external sources of BTC through the EGFR–PI3K–Akt–Erk pathway to the formation of inflammatory microenvironment. BTC may act as a potential target to monitor and improve the development of lung cancer inflammation.

【 授权许可】

   
2014 Shi et al.; licensee BioMed Central Ltd.

【 图 表 】

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