Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment

Vannitamby, A, Seow, H, Anderson, G, Vlahos, R, Thompson, M, Steinfort, D, Irving, L and Bozinovski, S 2017, 'Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment', eThorax, pp. 1-4.


Document type: Journal Article
Collection: Journal Articles

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Title Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment
Author(s) Vannitamby, A
Seow, H
Anderson, G
Vlahos, R
Thompson, M
Steinfort, D
Irving, L
Bozinovski, S
Year 2017
Journal name eThorax
Start page 1
End page 4
Total pages 4
Publisher BMJ Group
Abstract Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue. MMP-9 gene expression and immunohistochemistry identified tumour-associated neutrophils, but not macrophages, as a predominant source of this proteinase. In addition, PTEN gene expression was significantly reduced in tumour and there was evidence of epithelial MMP-9 expression. To explore whether PTEN can regulate epithelial MMP-9 expression, a small interfering (si)RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression.
Subject Respiratory Diseases
DOI - identifier 10.1136/thoraxjnl-2016-209389
ISSN 1468-3296
Additional Notes Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
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