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学科主题: 临床医学
题名:
Continual Exposure to Cigarette Smoke Extracts Induces Tumor-Like Transformation of Human Nontumor Bronchial Epithelial Cells in a Microfluidic Chip
作者: Li, Encheng1; Xu, Zhiyun1; Liu, Fen1; Wang, Huiling1; Wen, Jiabin1; Shao, Shujuan2; Zhang, Lichuan3; Wang, Lei4; Liu, Chong4; Lu, Jianxin5; Wang, Wenxin6; Gao, Zhancheng7; Wang, Qi1
关键词: Smoking ; Transformation ; Epithelial cells ; Reactive oxygen species ; Microfluidic chip
刊名: JOURNAL OF THORACIC ONCOLOGY
发表日期: 2014-08-01
卷: 9, 期:8, 页:1091-1100
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Respiratory System
研究领域[WOS]: Oncology ; Respiratory System
关键词[WOS]: OBSTRUCTIVE PULMONARY-DISEASE ; LUNG-CANCER ; OXIDATIVE STRESS ; DOWN-REGULATION ; FOLLOW-UP ; INFLAMMATION ; ACTIVATION ; PROLIFERATION ; TUMORIGENESIS ; SENSITIVITY
英文摘要:

Introduction: Heavy cigarette smoking-related chronic obstructive pulmonary disease is an independent risk factor for lung squamous carcinoma. However, the mechanisms underlying the malignant transformation of bronchial epithelial cells are unclear.

Methods: In our study, human tumor-adjacent bronchial epithelial cells were obtained from 10 cases with smoking-related chronic obstructive pulmonary disease and lung squamous carcinoma and cultured in an established microfluidic chip for continual exposure to cigarette smoke extracts (CSE) to investigate the potential tumor-like transformation and mechanisms. The integrated microfluidic chip included upstream concentration gradient generator and downstream cell culture chambers supplied by flowing medium containing different concentrations of CSE.

Results: Our results showed that continual exposure to low doses of CSE promoted cell proliferation whereas to high doses of CSE triggered cell apoptosis. Continual exposure to CSE promoted reactive oxygen species production in human epithelial cells in a dose-dependent manner. More importantly, continual exposure to low dose of CSE promoted the epithelial-to-mesenchymal transition process and anchorage-independent growth, and increased chromosome instability in bronchial epithelial cells, accompanied by activating the GRP78, NF-kappa B, and PI3K pathways.

Conclusions: The established microfluidic chip is suitable for primary culture of human tumor-adjacent bronchial epithelial cells to investigate the malignant transformation. Continual exposure to low doses of CSE promoted tumor-like transformation of human nontumor bronchial epithelial cells by inducing reactive oxygen species production and activating the relevant signaling.

语种: 英语
WOS记录号: WOS:000340138700010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63971
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Dalian Med Univ, Affiliated Hosp 2, Dept Resp Med, Dalian, Peoples R China
2.Dalian Med Univ, Dept Histol & Embryol, Dalian, Peoples R China
3.Dalian Univ, Affiliated Zhongshan Hosp, Dept Resp Med, Dalian 116012, Peoples R China
4.Dalian Univ Technol, Key Lab Micro Nano Technol & Syst Liaoning Prov, Dalian, Peoples R China
5.Wenzhou Med Coll, Key Lab Lab Med, Zhejiang Prov Key Lab Med Genet, Minist Educ, Wenzhou, Zhejiang, Peoples R China
6.Univ Coll Dublin, Sch Med & Med Sci, Charles Inst Dermatol, Dublin, Ireland
7.Peking Univ, Peoples Hosp, Dept Resp & Crit Care Med, Beijing 100044, Peoples R China

Recommended Citation:
Li, Encheng,Xu, Zhiyun,Liu, Fen,et al. Continual Exposure to Cigarette Smoke Extracts Induces Tumor-Like Transformation of Human Nontumor Bronchial Epithelial Cells in a Microfluidic Chip[J]. JOURNAL OF THORACIC ONCOLOGY,2014,9(8):1091-1100.
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