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Topics {✒️}

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Questions {❓}

• Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow?

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         headline:Interactions between neutrophils and non-small cell lung cancer cells: enhancement of tumor proliferation and inflammatory mediator synthesis
         description:The inflammatory tumor microenvironment plays a crucial role in tumor progression. In lung cancer, both bacterial infections and neutrophilia are associated with a poor prognosis. In this study, we characterized the effect of isolated human neutrophils on proliferation of the non-small cell lung cancer (NSCLC) cell line A549 and analyzed the impact of A549–neutrophil interactions on inflammatory mediator generation in naive and lipopolysaccharide (LPS)-exposed cell cultures. Co-incubation of A549 cells with neutrophils induced proliferation of resting and LPS-exposed A549 cells in a dose-dependent manner. In transwell-experiments, this effect was demonstrated to depend on direct cell-to-cell contact. This pro-proliferative effect of neutrophils on A549 cells could be attenuated by inhibition of neutrophil elastase activity, but not by oxygen radical neutralization. Correspondingly, neutrophil elastase secretion, but not respiratory burst, was specifically enhanced in co-cultures of A549 cells and neutrophils. Moreover, interference with COX-2 activity by indomethacin or the specific COX-2 inhibitor NS-398 also blunted the increased A549 proliferation in the presence of neutrophils. In parallel, a massive amplification of COX-2-dependent prostaglandin E2 synthesis was detected in A549–neutrophil co-cultures. These findings suggest that direct cell–cell interactions between neutrophils and tumor cells cause release of inflammatory mediators which, in turn, may enhance tumor growth in NSCLC.
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      description:The inflammatory tumor microenvironment plays a crucial role in tumor progression. In lung cancer, both bacterial infections and neutrophilia are associated with a poor prognosis. In this study, we characterized the effect of isolated human neutrophils on proliferation of the non-small cell lung cancer (NSCLC) cell line A549 and analyzed the impact of A549–neutrophil interactions on inflammatory mediator generation in naive and lipopolysaccharide (LPS)-exposed cell cultures. Co-incubation of A549 cells with neutrophils induced proliferation of resting and LPS-exposed A549 cells in a dose-dependent manner. In transwell-experiments, this effect was demonstrated to depend on direct cell-to-cell contact. This pro-proliferative effect of neutrophils on A549 cells could be attenuated by inhibition of neutrophil elastase activity, but not by oxygen radical neutralization. Correspondingly, neutrophil elastase secretion, but not respiratory burst, was specifically enhanced in co-cultures of A549 cells and neutrophils. Moreover, interference with COX-2 activity by indomethacin or the specific COX-2 inhibitor NS-398 also blunted the increased A549 proliferation in the presence of neutrophils. In parallel, a massive amplification of COX-2-dependent prostaglandin E2 synthesis was detected in A549–neutrophil co-cultures. These findings suggest that direct cell–cell interactions between neutrophils and tumor cells cause release of inflammatory mediators which, in turn, may enhance tumor growth in NSCLC.
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            type:Organization
      name:Ulrich Grandel
      affiliation:
            name:University of Giessen and Marburg Lung Center (UGMLC)
            address:
               name:Department of Internal Medicine IV/V, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Internal Medicine IV/V, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
      name:Department of Internal Medicine IV/V, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
      name:Department of Anaesthesiology, University of Giessen, Giessen, Germany
      name:Department of Internal Medicine IV/V, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
      name:Department of Internal Medicine II, Biostatistics Group, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
      name:Department of Internal Medicine II, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
      name:Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
      name:Department of Radiotherapy and Radiooncology, Philipps-University, Marburg, Germany
      name:Department of Internal Medicine IV/V, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
      name:Department of Internal Medicine IV/V, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
      name:Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
      name:Department of Internal Medicine II, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
      name:Department of Internal Medicine IV/V, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
      name:Department of Internal Medicine IV/V, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany

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