Osteopontin Expression in Small Airway Epithelium in Copd is Dependent on Differentiation and Confined to Subsets of Cells

Abstract

Osteopontin (OPN) plays a role in inflammation via recruitment of neutrophils and tissue remodeling. In this study, we investigated the distribution of OPN-expressing cells in the airway epithelium of normal lung tissue and that from patients with chronic obstructive pulmonary disease (COPD). OPN was detected on the epithelial cell surface of small airways and in scattered cells within the epithelial cell layer. Staining revealed higher OPN concentrations in tissue showing moderate to severe COPD compared to that in controls. In addition, OPN expression was confined to goblet and club cells, and was absent from ciliated and basal cells as detected via immunohistochemistry. However, OPN expression was up-regulated in submerged basal cells cultures exposed to cigarette smoke (CS) extract. Cell fractioning of air-liquid interface cultures revealed increased OPN production from basal compartment cells compared to that in luminal fraction cells. Furthermore, both constitutive and CS-induced expression of OPN decreased during differentiation. In contrast, cultures stimulated with interleukin (IL)-13 to promote goblet cell hyperplasia showed increased OPN production in response to CS exposure. These results indicate that the cellular composition of the airway epithelium plays an important role in OPN expression and that these levels may reflect disease endotypes in COPD.

High expression of SPP1 in patients with chronic obstructive pulmonary disease (COPD) is correlated with increased risk of lung cancer

“…On the other hand, SPP1 is associated with neutrophilic inflammation and emphysema [30]. Cigarette smoking can increase SPP1 expression in induced sputum, and its level is increased in induced sputum [31] and lung tissue [32] of patients with COPD. Hence, SPP1 may participate in the pathogenesis of COPD.…”

Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses

“…OPN contributes to processes of tissue remodeling and EMT during tumor progression, for example, renal tubular epithelial cells, hepatocellular carcinomas, or breast carcinomas 15,16 . Our previous studies demonstrated that OPN gene and protein overexpressed in acute exacerbation of chronic obstructive pulmonary disease and lung cancer are probably responsible for evolution and heterogeneity of lung cancer 17,18 . OPN overexpression was considered as an independent prognostic factor in patient overall survival and associated with more aggressive phenotypes of patients with lung cancer, 19 although the molecular mechanisms are still unclear.…”

Lipopolysaccharide and lipoteichoic acid regulate the PI3K/AKT pathway through osteopontin/integrin β3 to promote malignant progression of non-small cell lung cancer

“…It can be alternatively spliced to produce a variety of local functions, such as tumor growth, invasion, metastasis, angiogenesis, drug resistance, and immunosuppression. It is widely expressed in bone, kidney, breast, thymus, the immune system, and the brain ( 16 ). The most versatile subtype in tumor tissue is β3 ( 17 ), which is related to growth, invasion, metastasis, and survival.…”