Source: Annual Congress 2010 - Pathology of lung cancer
Disease area: Thoracic oncology

Abstract

Background: Bacterial infections are common in NSCLC and growing evidence indicates that inflammation is contributing to cancer growth.
Aims and objectives: Against this background, we investigated the effect of the bacterial cell wall components LPS on the proliferation of the NSCLC cell line A549 in vitro.
Methods: Proliferation of A549 cells was quantified by MTS-assay. PGE₂ production was analyzed by ELISA and COX-2 transscripts were quantified by RT-PCR.
Results: Incubation of A549 cells with LPS induced a time- and dose-dependent proliferation of A549 cells. Pro-proliferative effects of endotoxin could be inhibited by neutralizing antibodies targeting CD14 and TLR4, but not by inhibition of TLR2. Interestingly, interference with COX-2 activity by the specific inhibitor NS-398 strongly attenuated the LPS-induced tumor cell proliferation. In parallel, large amounts of COX-2 dependent PGE₂ were released by LPS-stimulated A549 cells. Moreover, enhanced transcription of COX-2 specific mRNA was detected in LPS-stimulated A549 cells. Interestingly, EGFR signaling was obviously involved in LPS-induced tumor cell proliferation and PGE₂ release, as both effects could be inhibited by the neutralizing EGFR-antibody cetuximab.
Conclusions: We conclude that LPS induces COX-2 dependent proliferation of A549 cells in a CD14, TLR4, and EGFR dependant manner. These effects might contribute to pathogen induced tumor proliferation in NSCLC.

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K. Hattar, R. Savai, G. A. Banat, R. T. Schermuly, L. Fink, W. Seeeger, F. Grimminegr, U. Sibelius, U. Grandel (Giessen, Germany). Endotoxin induces proliferation of NSCLC cells by a COX-2 dependent manner – Role of CD14, TLRs and EGFR signaling. Eur Respir J 2010; 36: Suppl. 54, 3265

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