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CXCL12和CXCR4而非CXCR7主要由头颈部鳞状细胞癌的基质表达。

CXCL12 and CXCR4, but not CXCR7, are primarily expressed by the stroma in head and neck squamous cell carcinoma.

作者信息

Clatot Florian, Cornic Marie, Berghian Anca, Marchand Vinciane, Choussy Olivier, El Ouakif Faissal, François Arnaud, Ruminy Philippe, Laberge-Le-Couteulx Sophie, Picquenot Jean-Michel, Jardin Fabrice

机构信息

1Department of Medical Oncology, Centre Henri Becquerel, IRON, Rouen 2INSERM U918, Centre Henri Becquerel, IRIB, Rouen 3Department of Pathology, Centre Henri Becquerel, Rouen 4Department of Head and Neck Surgery, Hospital Charles Nicolle, Rouen 5Department of Head and Neck Surgery, Centre Henri Becquerel, Rouen 6Department of Pathology, Hospital Charles Nicolle, Rouen, France.

出版信息

Pathology. 2015 Jan;47(1):45-50. doi: 10.1097/PAT.0000000000000191.

Abstract

The CXCL12/CXCR4 axis is involved in numerous models of metastatic dissemination, including head and neck squamous cell carcinoma (HNSCC). We assessed the relative expressions of CXCL12, CXCR4 and CXCR7 in the stroma and the tumour of HNSCC, and evaluated the methylation status of the CXCL12 promoter.Snap-frozen, HPV negative HNSCC samples were micro-dissected to isolate the tumoural and stromal compartments. The expression levels of CXCL12, CXCR4 and CXCR7 were assessed by qRT-PCR, and the methylation level of the CXCL12 promoter was evaluated by pyrosequencing.In total, 23 matched tumour/stroma samples were analysed. Higher expressions of CXCR4 and CXCL12 were observed in the stroma (p = 0.012 and p < 0.0001, respectively). No significant difference in expression was observed for CXCR7. A high methylation level (>40%) of the CXCL12 promoter was observed in only a few tumoural samples (5/23) and was associated with a lower expression of the gene (p = 0.03).Stromal cells, rather than the tumour itself, are mainly responsible for the expression of both CXCL12 and CXCR4 expression in HNSCC. CXCR7 expression did not differ between the two compartments and was not related to CXCL12 or CXCR4 expression. Finally, the methylation of the CXCL12 promoter could only explain the low intra-tumoural expression of this gene in 20% of cases.

摘要

CXCL12/CXCR4轴参与了包括头颈部鳞状细胞癌(HNSCC)在内的多种转移扩散模型。我们评估了CXCL12、CXCR4和CXCR7在HNSCC基质和肿瘤中的相对表达,并评估了CXCL12启动子的甲基化状态。对HPV阴性的HNSCC样本进行速冻切片,通过显微切割分离肿瘤和基质部分。采用qRT-PCR检测CXCL12、CXCR4和CXCR7的表达水平,采用焦磷酸测序法评估CXCL12启动子的甲基化水平。总共分析了23对匹配的肿瘤/基质样本。在基质中观察到CXCR4和CXCL12的表达较高(分别为p = 0.012和p < 0.0001)。CXCR7的表达未观察到显著差异。仅在少数肿瘤样本(5/23)中观察到CXCL12启动子的高甲基化水平(>40%),且与该基因的低表达相关(p = 0.03)。在HNSCC中,基质细胞而非肿瘤本身主要负责CXCL12和CXCR4的表达。两个部分之间的CXCR7表达没有差异,且与CXCL12或CXCR4表达无关。最后,CXCL12启动子的甲基化仅能解释20%病例中该基因在肿瘤内的低表达。

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