Interactions between neutrophils and NSCLC cells in vitro effects on neutrophil inflammatory mediator generation and tumour cell proliferation

e22148 Background: Growing evidence indicates that interactions between tumour cells and the inflammatory cellular microenvironment are crucial for tumour biology. In NSCLC, both bacterial infections and leukocytosis are associated with a poor prognosis. Against this background, we studied the effect of normal bronchial epithelial cells (B2B) and NSCLC cells (A549) on inflammatory neutrophil behaviour and quantified tumour cell proliferation in the presence of neutrophils. Methods: Isolated human neutrophils were co-cultured with B2B or A549 cells. Neutrophil respiratory burst was quantified by cytochrome C reduction and elastase activity was measured by the kinetics of 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 the bacterial tripeptide fMLP. In contrast, when co-cultured with B2B cells, these inflammatory neutrophil reactions were blunted. This could be attributed to release of NO and adenosine by the B2B cells. The increase of oxygen radical release and elastase degranulation in the presence of A549 cells was mediated by direct cell-to-cell contact. COX-2 dependent prostanoids were obviously involved in the activation of inflammatory neutrophil behaviour, as shown by the inhibitory capacity of the COX-2 specific inhibitor NS-398 in the co-culture system. Interestingly, activated neutrophils induced proliferation of NSCLC cells in a dose-dependent manner. Conclusions: The reciprocal interactions between neutrophils and NSCLC cells may enhance neutrophil-derived tissue destruction and tumour growth under inflammatory conditions. No significant financial relationships to disclose.