title: Macrophages promote benzopyrene-induced tumor transformation of human bronchial epithelial cells by activation of NF-κB and STAT3 signaling in a bionic airway chip culture and in animal models.
abstract: We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation of human bronchial epithelial cells using a BaP-induced tumor transformation model with a bionic airway chip in vitro and in animal models. The bionic airway chip culture data showed that macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-κB and STAT3 pathways to induce cell proliferation, colony formation in chip culture, and tumorigenicity in nude mice. Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture. In vivo, macrophages promoted lung tumorigenesis in a carcinogen-induced animal model. Similarly, blockage of NF-κB, STAT3, or cyclinD1 using siRNA transfection decreased the carcinogen-induced tumorigenesis in rats. We demonstrated that macrophages are critical in promoting lung tumorigenesis and that the macrophage-initiated TNF-α/NF-κB/cyclinD1 and IL-6/STAT3/cyclinD1 pathways are primarily responsible for promoting lung tumorigenesis.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Encheng
authors.initials: E
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Physical Examination Center, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Sun
authors.affiliation: The Liaoning Provincial Key Laboratory for Micro/Nano Technology, Dalian University of Technology, Dalian, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Respiratory & Critical Care Medicine, The People's Hospital of Peking University, Beijing, China.
authors.forename: Zhancheng
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000368:Aged; D000818:Animals; D001564:Benzo(a)pyrene; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002452:Cell Count; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D056656:Lab-On-A-Chip Devices; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
chemical_list: D001564:Benzo(a)pyrene; D019938:Cyclin D1; D015850:Interleukin-6; D016328:NF-kappa B; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C530104:CCND1 protein, human; C508600:IL6 protein, human; C494086:STAT3 protein, human; C494088:Stat3 protein, rat
keywords: NF-κB; STAT3; macrophages; malignant transformation; microfluidic chip
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