Expression patterns of endothelin-1 and its receptors in colorectal cancer

Expression patterns of endothelin-1 and its receptors in colorectal cancer
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DOI:
10.1002/jso.23017
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发表时间:
2012-06-01
影响因子:
2.5
通讯作者:
Rassidakis, George Z.
Rassidakis, George Z.
中科院分区:
医学3区
文献类型:
--
作者:
Liakou, Paraskevi;Tepetes, Kostantinos;Rassidakis, George Z.

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背景与目的内皮素-1 (ET-1)是一种有效的血管收缩肽,在肿瘤发生中起重要作用。先前的体外研究表明,结直肠癌细胞产生ET-1。方法:采用Western blot和免疫组化方法对结直肠癌细胞系和肿瘤中ET-1及其受体ET-A (ETAR)和ET-B (ETBR)进行分析。同时,采用ELISA法测定肿瘤切除前后血液样本中ET-1水平。结果:39例肿瘤细胞均有不同水平的ET-1免疫组织化学表达。邻近正常黏膜ET-1表达为阴性。肿瘤组织周围浸润较深的区域ETAR表达与肿瘤分期有显著相关性。ETBR水平非常低或检测不到。Western blot分析结直肠癌的配对(正常,肿瘤)新鲜冷冻样本和四种结肠癌细胞系证实了这些发现。此外,ELISA发现肿瘤切除后外周循环中ET-1水平较术前低。结论:ET-1和ETAR在原代和培养结肠癌细胞中的表达水平高于正常结肠粘膜细胞,而ETBR在培养结肠癌细胞中的表达水平高于正常结肠粘膜细胞。ET-1/ETAR轴在结肠癌发生中的作用有待进一步的功能研究。中华外科杂志。2012;105: 643 - 649。(C) 2011 Wiley期刊公司
Background and Objectives Endothelin-1 (ET-1), a potent vasoconstricting peptide, plays an important role in carcinogenesis. Previous in vitro studies have shown that colorectal cancer cells produce ET-1.Methods: ET-1 and its receptors ET-A (ETAR) and ET-B (ETBR) were analyzed in colorectal cancer cell lines and tumors by Western blot and immunohistochemistry. Also, ET-1 levels were measured by ELISA in blood samples collected before and after tumor resection.Results: ET-1 was immunohistochemically expressed by tumor cells at a variable level in 39 cases tested. The adjacent normal mucosa was negative for ET-1 expression. Strong ETAR expression observed in the deeper infiltrating areas at the periphery of neoplastic tissue correlated significantly with tumor stage. ETBR levels were very low or undetectable. Western blot analysis in paired (normal, tumor) fresh-frozen samples of colorectal cancers and in four colon carcinoma cell lines confirmed these findings. In addition, lower levels of ET-1 in the peripheral circulation after the tumor resection were found by ELISA as compared to those observed before surgery.Conclusions: ET-1 and ETAR, but not ETBR, are expressed at a higher level in primary and cultured colon carcinoma cells as compared to normal colon mucosa cells. Further functional studies are needed to explore the role of ET-1/ETAR axis in colon carcinogenesis. J. Surg. Oncol. 2012; 105: 643-649. (C) 2011 Wiley Periodicals, Inc.