Epigenetics Underpinning the Regulation of the CXC ELR Chemokines in Non-Small Cell Lung CancerReportar como inadecuado




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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.



Autor: Anne-Marie Baird, Steven G. Gray, Kenneth J. O-Byrne

Fuente: http://plos.srce.hr/



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