Abstract
Chronic obstructive pulmonary disease (COPD) is a risk factor for the development of lung cancer (LC). The mechanism of interplay between both diseases remains poorly recognized. This report examines whether COPD may cause a senescence response in human bronchial epithelial cells (HBECs), leading to the progression of LC in a senescence-dependent manner. The results show that HBECs exposed to serum from COPD patients manifest increased expression of markers of cellular senescence, including senescence-associated β-galactosidase (SA-β-Gal), histone γ-H2A.X, and p21, as compared to the serum of healthy donors. This effect coincides with an increased generation of reactive oxygen species by these cells. The clinical analysis demonstrated that COPD may cause the senescence, independently on smoking status and disease severity. The concentrations of CXCL5, CXCL8/IL-8 and VEGF were higher in conditioned medium (CM) harvested from HBECs after exposure to COPD serum as compared to controls. In addition, CM treated with serum from COPD patients stimulated adhesion of A549 cancer cells to HBECs, as well as accelerating cancer cell proliferation and migration in vitro. Collectively, these findings indicate that COPD may induce senescence-like changes in HBECs and thus enhance some processes associated with the progression of lung cancer.
Highlights
Recent evidence suggests that some lung pathologies caused by environmental factors may be related to the development of cellular senescence[1,2]
We decided to take human bronchial epithelial cells (HBECs) for an experimental model because the majority of lung cancers are carcinomas that develop from the epithelial cells lining the airways[21]
In this study we focused our attention on three proteins, VEGF, CXCL8/IL-8 and CXCL5, whose overproduction has already been described in the case of various types of senescent cells[33]
Summary
Recent evidence suggests that some lung pathologies caused by environmental factors may be related to the development of cellular senescence[1,2]. It has been demonstrated that cellular senescence plays an important role in the progression of primary and metastatic tumors. 23% of lung cancer patients were previously diagnosed with COPD12. Patients with obstructive disease develop lung tumors two to four times more frequently than do healthy smokers. The coexistence of both diseases, as well as our knowledge of the potential role of cellular senescence in the pathogenesis of COPD and lung cancer, is suggestive of their joint pathogenesis. It is reasonable to determine whether COPD may elicit a senescence response in human bronchial epithelial cells (HBECs), leading implicitly to the progression of lung cancer in a senescence-dependent mechanism
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