67P - Investigation of the interaction between non-small cell lung cancer cells and immortalised normal bronchial epithelial cells

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Kenneth O'Byrne
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors K. O'Byrne1, M.P. Barr2, A. Urquhart3, S. Ryan4, S.G. Gray2, A. Davies3, D. Richard5, K. Gately2, A. Baird4
  • 1Princess Alexandra Hospital And Queensland University Of Technology, Cancer and Ageing Research Program, QLD 4102 - Brisbane/AU
  • 2Thoracic Oncology, St James's Hospital, D8 - Dublin/IE
  • 3Translational Cell Imaging Queensland, Queensland University of Technology, QLD 4102 - Brisbane/AU
  • 4Cancer And Ageing Research Program And Translational Cell Imaging Queensland, Queensland University of Technology, Brisbane/AU
  • 5Institute Of Health And Biomedical Innovation, Cancer And Ageing Research Program, Queensland University of Technology, Brisbane/AU

Abstract

Background

Non-small cell lung cancer consists of a diverse range of molecular and pathological features. This may be due in part to the critical interaction between normal and lung cancer cells. Consequently resulting in ‘normal’ cells acting in a malignant fashion. This project aims to identify pathways responsible for this altered ‘normal’ behaviour.

Methods

The normal bronchial epithelial cell line, HBEC4, was cultured in a trans-well co-culture system with a number of NSCLC cell lines. These included A549 (adenocarcinoma), SK-MES-1 (squamous cell carcinoma) and H460 (large cell carcinoma) cells. After seven days of culture, the HBEC4 cells were characterised using a number of different assays: cellular viability (Cytell), proliferation (BrdU ELISA), cell cycle (Cytell) and the gene expression profile was assessed for inflammatory and stem cell factor mediators (RT-PCR). In addition, a large miRNA screen was performed (Nanostring). Cancer exosomes were also isolated and their effect on HBEC4 proliferation was evaluated.

Results

After seven days of NSCLC exposure, HBEC4 cells displayed a number of phenotypic and genotypic modifications. This included significantly amplified cellular viability, proliferation and alterations in cell cycle progression. The gene expression profile of inflammatory mediators such as the TLRs and the Yamanaka factors (KFL4, Oct, c-myc) were significantly elevated. The miRNA expression profile varied depending on which NSCLC subtype the HBEC4 cell line was exposed to. However miRNA target genes included those related to pathways involved in inflammation, cell cycle and proliferation amongst others. HBEC4 proliferation was also increased in response to cancer exosome fractions. Currently, experiments are ongoing to assess this co-culture system within a 3D culture setting.

Conclusions

Cancer cells may promote significant genotypic and phenotypic changes within the normal lung epithelium through various means. Soluble factors and/or cancer-secreted vesicles such as exosomes may facilitate these modifications. This relationship may contribute to the diverse molecular make up of lung cancer tumours and in turn affect patient response to both conventional and targeted therapies.

Clinical trial identification

Legal entity responsible for the study

Queensland University of Technology

Funding

Queensland Health

Disclosure

All authors have declared no conflicts of interest.