Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer.
Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer.
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DOI：
10.1371/journal.pone.0014593
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发表时间：
2011-01-27
期刊：
影响因子：
3.7
通讯作者：
O'Byrne KJ
中科院分区：
文献类型：
--
作者：
Baird AM;Gray SG;O'Byrne KJ
血管生成可能在非小细胞肺癌(NSCLC)的发病机制中起作用。CXC(ELR+)趋化因子家族是血管生成反应的强大促进剂。检测CXC(ELR+)家族成员CXCL1-3/GROα-γ、CXCL8/IL-8、CXCR1/2在一系列新鲜冷冻非小细胞肺癌肿瘤中的表达。此外，在正常的支气管上皮和NSCLC细胞系中检测了这些趋化因子的表达和表观遗传调节。总体而言，与正常相比，肿瘤组织中趋化因子配体(CXCL1、2、8)及其受体(CXCR1/2)的表达下调，但CXCL3除外。CXCL8和CXCR1/2受组蛋白翻译后修饰的表观遗传调控。重组CXCL8对正常支气管上皮细胞和鳞癌细胞株(SKMES-1)均无刺激作用。然而，在治疗72小时后观察到腺癌细胞株的增加。CXC(ELR+)趋化因子在非小细胞肺癌中表达异常。这些趋化因子的平衡在肿瘤微环境中可能是至关重要的，需要进一步阐明。表观遗传学靶向这些通路是否是肺癌治疗的可行治疗选择仍有待观察。
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. 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. 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. 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.
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
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DOI：
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发表时间：
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