Invasive bronchial fibroblasts derived from asthmatic patients activate lung cancer A549 cells in vitro

Ryszawy,Damian; Rolski,Filip; Ryczek,Karolina; Catapano,Jessica; Wróbel,Tomasz; Michalik,Marta; Czyż,Jarosław

doi:10.3892/ol.2018.9462

Invasive bronchial fibroblasts derived from asthmatic patients activate lung cancer A549 cells in vitro

Authors:
- Damian Ryszawy
- Filip Rolski
- Karolina Ryczek
- Jessica Catapano
- Tomasz Wróbel
- Marta Michalik
- Jarosław Czyż
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Affiliations: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30‑387 Kraków, Poland
Published online on: September 19, 2018 https://doi.org/10.3892/ol.2018.9462
Pages: 6582-6588
Copyright: © Ryszawy et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epidemiological data suggests that there are functional links between bronchial asthma and lung carcinogenesis. Bronchial fibroblasts serve a prominent role in the asthmatic process; however, their involvement in lung cancer progression remains unaddressed. To estimate the effect of the asthmatic microenvironment on the invasiveness of lung cancer cells, the present study compared the behavior of human non‑small cell lung cancer A549 cells exposed to the signals from human bronchial fibroblasts (HBFs) derived from non‑asthmatic donors (NA HBFs) and from asthmatic patients (AS HBFs). NA HBFs did not significantly affect A549 motility, whereas AS HBFs and the media conditioned with AS HBF/A549 co‑cultures increased Snail‑1/connexin43 expression and motility of A549 cells. In contrast to NA HBFs, which formed A549‑impenetrable lateral barriers, α‑SMA+ AS HBFs actively infiltrated A549 monolayers and secreted chemotactic factors that arrested A549 cells within AS HBF/A549 contact zone. However, small sub‑populations of A549 cells could release from this arrest and colonize distant regions of AS HBF monolayers. These data indicated that the interactions between lung cancer cells and HBFs in asthmatic bronchi may facilitate the colonization of lung tumors by fibroblasts. It further stabilizes the tumor microenvironment and potentially facilitates collective colonization of novel bronchial loci by cancer cells. Potential mechanistic links between the asthmatic process and lung cancer progression suggest that bronchial asthma should be included in the list of potential prognostic markers for lung cancer therapy.

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