7: Normal bronchial epithelial cells exhibit altered cellular behaviour when exposed to lung cancer cells in a co-culture system

Introduction: Non-small cell lung cancer is a complex solid tumour displaying significant heterogeneity between patients. Cancer cells may influence the behaviour of adjacent normal cells and this may contribute to the complexity of this disease. The objective of this study was to improve our understanding of this relationship. Methods: A normal bronchial epithelial cell line (HBEC4) was exposed to adenocarcinoma (A549), large cell (H460) and squamous (SK-MES-1) non-small cell lung cancer cell lines for a period of seven days in a transwell co-culture system. Subsequently, the HBEC4 cells were assessed for alterations in cellular behaviour (viability/apoptosis/cell cycle/exosome response) and changes in gene expression (RT-PCR/miRNA). Results: Following seven days of co-culture, the HBEC4 cells displayed changes in cell number, cellular viability and cell cycle. No significant differences in apoptosis were detected. Gene expression profiles were altered in inflammatory and stem cell pathways, with no changes in NSCLC subtype markers detected. In addition, a unique pattern of miRNA expression was observed in the HBEC4 cells. This varied depending on NSCLC exposure. Conclusion: Lung cancer cells can alter the behavior of normal bronchial epithelial cells through multiple mechanisms. This may contribute to the heterogeneity observed in this disease.