title: Cigarette smoke-induced disruption of pulmonary barrier and bacterial translocation drive tumor-associated inflammation and growth.
abstract: Microorganisms have an important role in tumorgenesis by the induction of inflammation and by a direct impact on tumor cells. Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for lung cancer and microbial colonization. We asked whether bacterial pathogens act as tumor promoters during CS-induced pulmonary inflammation. In a metastatic lung cancer (LC) model, Lewis lung carcinoma (LLC) cells were injected in mice to initiate the growth of tumors in the lung. Exposure to the combination of cigarette smoke (CS) and nontypeable Haemophilus influenzae (NTHi) synergistically increased metastatic growth. Lung levels of albumin and LDH, translocation of bacterial factors into tumor tissue, tumor inflammation, and tumor proliferation were significantly increased in mice exposed to CS in combination with NTHi. Bacterial pathogens increased the proliferation of cultured LLC cells and human cancer cell lines. Metastatic growth induced by the exposure to CS in combination with NTHi was reduced in mice deficient for IL-17. Our data provide evidence that CS-induced loss of pulmonary barrier integrity allows bacterial factors to translocate into tumor tissue and to regulate tumor-associated inflammation and tumor proliferation. Translocation of bacterial factors in tumor tissue links CS-induced inflammation with tumor proliferation.
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Jungnickel
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wonnenberg
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Karabiber
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Voss
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Wolf
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Honecker
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kamyschnikow
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Herr
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Bals
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany christoph.beisswenger@uks.eu.
authors.forename: C
authors.initials: C
authors.lastname: Beisswenger
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000382:microbiology / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012907:Smoking / Q000009:adverse effects*; D047368:Tumor Burden
keywords: COPD; IL-17; bacterial pathogens; bacterial translocation; cigarette smoke; lung cancer; lung metastasis; tumor growth