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.

Cigarette smoke and electronic cigarettes differentially activate bronchial epithelial cells

“…In the present study we did not observe a change in antimicrobial activity or barrier integrity after exposure of differentiated airway epithelium to ECIG-vapor. The results from the TCIG-exposed cells are in line with previous reports that TCIG-smoke leads to a defect in host defense and disruption of the epithelial barrier in vivo and in vitro [27,34,43]. We showed earlier that smoking is associated with reduced concentrations of hBD2 in airway secretions of patients with community acquired pneumonia, and that exposure of differentiated pHBE to volatile TCIG-smoke leads to a decreased expression and synthesis of hBD2 after infection with bacteria and an increased inflammatory reaction [27].…”

“…ECIG has no effect on host defense TCIG smoke is known to inhibit the host defense activities of epithelial cells and is a major risk factor for respiratory tract infections [27,34]. To determine whether ECIGs have an effect on epithelial host defense, we exposed human Calu3 cells to TCIG or the corresponding amount of ECIG-vapor and infected the cells with 1 × 10 3 CFU P. aeruginosa.…”

“…To analyse the epithelial barrier integrity, the translocation of dextran from the apical to the basolateral side of the cell layer was determined as described before [34]. Directly after exposures, 200 μL of 10 mg/mL fluorescein labeled isothiocyanate-dextran (FITC-Dextran, 70 kDa, Sigma-Aldrich, Munich, Germany) in PBS or PBS containing heat inactivated P. aeruginosa PAO1 were applied directly on cells.…”

Lung inflammation and disease: A perspective on microbial homeostasis and metabolism

“…An interesting piece of supporting evidence for this view was discovered by Jungnickel et al (67). This study used a lung carcinoma model in which lung carcinoma cells were injected in mice.…”

Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke

“…Naive RAGE -/- mice had significantly increased concentrations of albumin in their BALF. Leakage of serum proteins from the blood into the lung indicates an endothelial-epithelial barrier defect in RAGE -/- mice [34, 38–40]. Other studies using increased total protein content in the BALF of mice as a marker for barrier dysfunction could not determine any differences between WT and RAGE -/- mice [36, 41, 42].…”