title: Promotion of a cancer-like phenotype, through chronic exposure to inflammatory cytokines and hypoxia in a bronchial epithelial cell line model.
abstract: Globally, lung cancer accounts for approximately 20% of all cancer related deaths. Five-year survival is poor and rates have remained unchanged for the past four decades. There is an urgent need to identify markers of lung carcinogenesis and new targets for therapy. Given the recent successes of immune modulators in cancer therapy and the improved understanding of immune evasion by tumours, we sought to determine the carcinogenic impact of chronic TNF-α and IL-1β exposure in a normal bronchial epithelial cell line model. Following three months of culture in a chronic inflammatory environment under conditions of normoxia and hypoxia (0.5% oxygen), normal cells developed a number of key genotypic and phenotypic alterations. Important cellular features such as the proliferative, adhesive and invasive capacity of the normal cells were significantly amplified. In addition, gene expression profiles were altered in pathways associated with apoptosis, angiogenesis and invasion. The data generated in this study provides support that TNF-α, IL-1β and hypoxia promotes a neoplastic phenotype in normal bronchial epithelial cells. In turn these mediators may be of benefit for biomarker and/or immune-therapy target studies. This project provides an important inflammatory in vitro model for further immuno-oncology studies in the lung cancer setting.
authors.affiliation: Cancer and Ageing Research Program, Queensland University of Technology, Brisbane, Australia.|Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, Ireland.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Baird
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, Ireland.|HOPE Directorate, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Gray
authors.affiliation: Cancer and Ageing Research Program, Queensland University of Technology, Brisbane, Australia.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Richard
authors.affiliation: Cancer and Ageing Research Program, Queensland University of Technology, Brisbane, Australia.|Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, Ireland.|Division of Cancer Services, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
mesh_terms: D015415:Biomarkers; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018836:Inflammation Mediators; D010100:Oxygen