Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer

Baird, Anne-Marie, Gray, Steven G., & O'Byrne, Kenneth J. (2011) Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer. PLoS ONE, 6(1), e14593.

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Abstract

Background: Angiogenesis may play a role in the pathogenesis of Non-Small Cell Lung cancer (NSCLC). The CXC (ELR+) chemokine family are powerful promoters of the angiogenic response.

Methods: The expression of the CXC (ELR+) family members (CXCL1-3/GROα-γ, CXCL8/IL-8, CXCR1/2) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of these chemokines was examined in normal bronchial epithelial and NSCLC cell lines.

Results: Overall, expression of the chemokine ligands (CXCL1, 2, 8) and their receptors (CXCR1/2) were down regulated in tumour samples compared with normal, with the exception of CXCL3. CXCL8 and CXCR1/2 were found to be epigenetically regulated by histone post-translational modifications. Recombinant CXCL8 did not stimulate cell growth in either a normal bronchial epithelial or a squamous carcinoma cell line (SKMES-1). However, an increase was observed at 72 hours post treatment in an adenocarcinoma cell line.

Conclusions: CXC (ELR+) chemokines are dysregulated in NSCLC. The balance of these chemokines may be critical in the tumour microenvironment and requires further elucidation. It remains to be seen if epigenetic targeting of these pathways is a viable therapeutic option in lung cancer treatment. © 2011 Baird et al.

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ID Code: 64810
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: chemokine, chemokine receptor CXCR1, chemokine receptor CXCR2, CXCL1 chemokine, CXCL2 chemokine, CXCL3 chemokine, interleukin 8, alpha chemokine, CXCL1 protein, human, CXCL2 protein, human, CXCL3 protein, human, IL8 protein, human, article, bronchus mucosa, cancer cell culture, cell growth, cell proliferation, chromatin immunoprecipitation, controlled study, CpG island, DNA methylation, down regulation, epigenetics, histone acetylation, human, human cell, human tissue, lung non small cell cancer, lung squamous cell carcinoma, protein expression, protein modification, reverse transcription polymerase chain reaction, tumor microenvironment, upregulation, biopsy, cell line, gene expression regulation, genetic epigenesis, genetics, lung tumor, metabolism, neovascularization (pathology), pathology, protein processing, tumor cell line, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Chemokine CXCL1, Chemokine CXCL2, Chemokines, CXC, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Humans, Interleukin-8, Lung Neoplasms, Neovascularization, Pathologic, Protein Processing, Post-Translational, Receptors, Interleukin-8A, Receptors, Interleukin-8B
DOI: 10.1371/journal.pone.0014593
ISSN: 1932-6203
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 2011 Baird et al.
Copyright Statement: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Deposited On: 26 Nov 2013 03:23
Last Modified: 05 Aug 2014 22:10

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