Serum from patients with chronic obstructive pulmonary disease promotes proangiogenic behavior of the vascular endothelium

B. Kuźnar-Kamińska, J. Mikuła-Pietrasik, E. Mały, N. Makowska, M. Malec, A. Tykarski, H. Batura-Gabryel, K. Książek

Department of Pulmonology, Allergology, and Respiratory Oncology, Poznań University of Medical Sciences, Poznań, Poland. kaminska@ump.edu.pl

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• Pharmacology

OBJECTIVE: It has been documented that COPD is a risk factor for lung cancer. In COPD patients, changes in lung angiogenesis – a critical process in the development of lung cancer – have been poorly investigated. We aimed to determine whether serum from COPD patients could promote the proangiogenic capabilities of endothelial cells in vitro.

PATIENTS AND METHODS: The research was carried out using sera from COPD patients and healthy volunteers, endothelial cells EA.hy926, and bronchial epithelial cells. The concentration of angiogenic molecules was quantified using ELISA tests. The proliferation and migration of EA.hy926 were tested using fluorescence-based methods. Tube formation was analyzed with a commercially available assay.

RESULTS: Sera from COPD patients and conditioned media generated by epithelial cells exposed to these sera stimulate proliferation, but not migration, of EA.hy926. This coincided with increased tube formation in both experimental regimens. The sera from COPD patients contained increased levels of CCL2, CCL21, and HGF, whereas the conditioned media generated by epithelial cells treated with these sera exhibited increased levels of CCL2, CCL21, CXCL8, FGF, and sICAM-1. The concentration of angiogenic markers in the sera and conditioned media, and their effect on the behavior of the endothelium were independent of smoking status (COPD and controls), stage of obstruction, and disease group (COPD).

CONCLUSIONS: The increased incidence of lung malignancy in COPD patients may be associated, at least to some extent, with the direct and indirect proangiogenic activity of their sera (via alterations in the secretome of epithelial cells).

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