Encheng Li1, Zhiyun Xu, Fen Liu, Huiling Wang, Jiabin Wen, Shujuan Shao, Lichuan Zhang, Lei Wang, Chong Liu, Jianxin Lu, Wenxin Wang, Zhancheng Gao, Qi Wang. 1. *Department of Respiratory Medicine, the Second Affiliated Hospital of Dalian Medical University; †Department of Histol&Embryol, Dalian Medical University, Dalian, China; ‡Department of Respiratory Medicine, the Affiliated Zhongshan Hospital of Dalian University; §Key laboratory for Micro/Nano Technology and System of Liaoning Province, Dalian University of Technology, Dalian; ‖Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou, Zhejiang, China; ¶The Charles Institute of Dermatology, School of Medicine and Medical Science, University College Dublin, Ireland; and #Department of Respiratory & Critical Care Medicine, the People's Hospital of Peking University, Beijing, China.
Abstract
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-κB, 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.
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, humantumor-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-κB, and PI3K pathways. CONCLUSIONS: The established microfluidic chip is suitable for primary culture of humantumor-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.
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Authors: Nicole M E Valle; Mariana P Nucci; Arielly H Alves; Luiz D Rodrigues; Javier B Mamani; Fernando A Oliveira; Caique S Lopes; Alexandre T Lopes; Marcelo N P Carreño; Lionel F Gamarra Journal: Cells Date: 2022-10-01 Impact factor: 7.666
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