P3.01-042 Lung Cancer Cells Can Stimulate Functional and Genotypic Modifications in Normal Bronchial Epithelial Cells
2017
Background: Normal lung epithelium cells may act in
concert with tumor cells, given that bystander effects may
exist between the two. This interaction may lead to inappropriate
activation of pro-oncogenic signaling pathways,
which may result in high mutational load and tumor heterogeneity.
The aim of this project is to evaluate the effects
of non-small cell lung cancer (NSCLC) cells on an immortalized
normal bronchial epithelial cell line.
Methods: A normal bronchial epithelial cell line (HBEC4)
was exposed to A549 (adenocarcinoma), H460 (large cell
carcinoma) and SK-MES-1 (squamous cell carcinoma)
NSCLC cell lines in a trans-well co-culture system. Cellular
characteristics were examined using a Cytell Cell Imaging
System (cell number, viability, apoptosis, cell cycle). The
gene expression profile was also determined in terms of
inflammatory mediators, stem cell markers (RT-PCR) and
miRNA profiling (Nanostring). The proliferative effect of
NSCLC cancer exosomes was also examined (BrdU ELISA)
on the HBEC4 cell line.
Results: A number of functional and gene modifications
were observed in the HBEC4 cell line after seven days of
co-culture. While patterns were similar amongst all
NSCLC subtypes, SK-MES-1 elicited the most significant
effects in terms of cell number, viability, cell cycle progression
and proliferative potential of isolated cancer
exosome fraction. Promotion of both inflammatory mediators
and stem cell marker expression was evident at
the mRNA level. There was no apparent consensus between
NSCLC subtypes and miRNA expression, as
exposure to each cell line resulted in distinct profiles of
miRNAs in HBEC4 cells. Bioinformatic analysis of miRNA
target genes, demonstrated that pathways such as p53,
MAPK, VEGF, TLR and Wnt were amongst those altered.
Conclusion: Cancer cells may promote significant
genotypic and phenotypic alterations within the normal
lung epithelium though multiple mechanisms. These
modifications may, in part, contribute to the heterogeneity
of lung cancer tumors and influence response to
both chemotherapeutics and targeted agents.
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