Source: Annual Congress 2010 - Pathology of lung cancer

Abstract

Background: Growing evidence indicates that interactions between tumor cells and the inflammatory cellular microenvironment are crucial for tumor biology. In NSCLC, both bacterial infections and leukocytosis are associated with a poor prognosis. Against this background, we studied the effect of NSCLC (A549)cells on neutrophil behaviour and quantified tumor cell proliferation in the presence of neutrophils.
Methods: Human neutrophils were co-cultured with A549 cells. Neutrophil respiratory burst was quantified by cytochrome C reduction and elastase activity was measured by substrate turnover. Proliferation of A549 cells was determined by MTS-assay.
Results: Co-culturing human neutrophils with A549 cells stimulated neutrophil respiratory burst and degranulation in response to fMLP. Co-incubation with neutrophils induced proliferation of resting and endotoxin-stimulated NSCLC cells in a dose-dependent manner. This effect was mediated by direct cell-to-cell contact. The effect of neutrophils on A549 proliferation could be attenuated by inhibition of neutrophil elastase, but not by oxygen radical neutralisation. Moreover, interference with COX activity by indomethacin as well as by the specific COX-2 inhibitor NS-398 blunted the increased A549 proliferation in PMN-A549 co-cultures. In parallel, as compared to mono-cultures of A549 cells and neutrophils, a massive amplification of COX-2 dependent PGE₂ synthesis was detected in endotoxin-stimulated A549-neutrophil co-cultures.
Conclusions: The interactions between neutrophils and NSCLC cells may enhance neutrophil-derived tissue destruction and tumor growth under inflammatory conditions.

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Citations should be made in the following way:
U. Grandel, K. Franz, M. Ludwig, W. Seeger, F. Grimminger, U. Sibelius, K. Hattar (Giessen, Germany). Interactions between neutrophils and NSCLC cells in vitro – effects on neutrophil inflammatory mediator generation and tumor cell proliferation. Eur Respir J 2010; 36: Suppl. 54, 3270

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