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结直肠癌中CXC受体的差异表达

Differential CXC receptor expression in colorectal carcinomas.

作者信息

Rubie C, Kollmar O, Frick V O, Wagner M, Brittner B, Gräber S, Schilling M K

机构信息

Department of General, Visceral, Vascular and Pediatric Surgery, University of the Saarland, Homburg/Saar, Germany.

出版信息

Scand J Immunol. 2008 Dec;68(6):635-44. doi: 10.1111/j.1365-3083.2008.02163.x. Epub 2008 Oct 6.

Abstract

In this study, we aimed to assess the expression profile of chemokine receptors CXCR1-4 in inflammatory and malignant colorectal diseases and corresponding hepatic metastases of synchronous and metachronous origin to elucidate their role in colorectal cancer (CRC) progression and metastasis. Chemokine receptor expression was assessed by quantitative real-time PCR, immunohistochemistry (IHC) and Western blot analysis in resection specimens from patients with ulcerative colitis (UC, n = 25), colorectal adenomas (CRA, n = 8), different stages of CRC (n = 48) as well as colorectal liver metastases (CRLM) along with their corresponding primary colorectal tumours (n = 16). While none of the chemokine receptors were significantly upregulated or downregulated in UC or CRA tissues, CXC receptors 1, 2 and 4 demonstrated a significant increase in expression in all tumour stages of CRC specimens with CXCR4 correlating with tumour grading (P < 0.05). On the other hand, CXCR3 showed no significant upregulation in either tumour stage, but significant overexpression in CRLM. While CXCR4 demonstrated significant upregulation in both tumour entities, IHC analysis revealed that the predominate cell type expressing CXCR4 in CRC is represented by tumour cells, whereas in CRLM the majority of positive CXCR4 signals is due to hepatocytes along the tumour invasion front. In conclusion, our findings show a very differential expression pattern of the four receptors in colorectal carcinomas and their corresponding liver metastases with prominent expression profiles that indicate a potential role in the pathogenesis of CRC.

摘要

在本研究中,我们旨在评估趋化因子受体CXCR1 - 4在炎症性和恶性结直肠疾病以及同步和异时性起源的相应肝转移中的表达谱,以阐明它们在结直肠癌(CRC)进展和转移中的作用。通过定量实时PCR、免疫组织化学(IHC)和蛋白质印迹分析,对溃疡性结肠炎(UC,n = 25)、结直肠腺瘤(CRA,n = 8)、不同阶段的CRC(n = 48)以及结直肠肝转移(CRLM)及其相应的原发性结直肠肿瘤(n = 16)患者的切除标本中的趋化因子受体表达进行评估。虽然在UC或CRA组织中,没有一种趋化因子受体显著上调或下调,但CXC受体1、2和4在CRC标本的所有肿瘤阶段均表现出表达显著增加,其中CXCR4与肿瘤分级相关(P < 0.05)。另一方面,CXCR3在任何肿瘤阶段均未显著上调,但在CRLM中显著过表达。虽然CXCR4在两种肿瘤实体中均显著上调,但IHC分析显示,CRC中表达CXCR4的主要细胞类型为肿瘤细胞,而在CRLM中,大多数CXCR4阳性信号是由于肿瘤侵袭前沿的肝细胞。总之,我们的研究结果显示了这四种受体在结直肠癌及其相应肝转移中的非常不同的表达模式,其突出的表达谱表明它们在CRC发病机制中具有潜在作用。

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