Functional expression of TRAIL receptors TRAIL-R1 and TRAIL-R2 in esophageal adenocarcinoma.
Functional expression of TRAIL receptors TRAIL-R1 and TRAIL-R2 in esophageal adenocarcinoma.
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TRAIL 受体 TRAIL-R1 和 TRAIL-R2 在食管腺癌中的功能表达。
DOI：
10.1016/j.ejca.2005.11.013
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Younes,Anas
中科院分区：
文献类型：
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作者：
Younes,Mamoun;Georgakis,GeorgiosV;Rahmani,Mahdis;Beer,David;Younes,Anas
肿瘤坏死因子相关的凋亡诱导配体(TRAIL/Apo2L)是肿瘤坏死因子超家族的一员，它优先诱导癌细胞的凋亡，而不诱导正常细胞的凋亡。TRAIL通过与其受体TRAIL-R1和TRAIL-R2相互作用而诱导细胞凋亡。最近，新的人源化激动型抗TRAIL-R1和抗TRAIL-R2抗体已经被开发出来，并正在进行I/II期临床试验。食管腺癌(EA)与严重的不良预后有关，在美国和西欧发病率迅速上升，几乎没有有效的非手术治疗。本研究的目的是确定人电针组织是否表达TRAIL-R1和/或TRAIL-R2，以及电针细胞株Bic-1和Seg-1是否表达功能性TRAIL-R1和/或TRAIL-R2。采用免疫组织化学方法(IHC)检测18例人电针组织中TRAIL-R1和TRAIL-R2的表达。16例(89%)表达TRAIL-R1，17例(94%)表达TRAIL-R2。免疫印迹分析、免疫组化和流式细胞仪检测发现两株细胞均表达TRAIL-R1和TRAIL-R2。全人激动型TRAIL-R1(HGS-ETR1)和TRAIL-R2(HGS-ETR2)抗体以时间和剂量依赖的方式诱导Bic-1和Seg-1细胞凋亡。我们的结果表明，绝大多数原代人类EA表达TRAIL-R1和TRAIL-R2，并且EA细胞系表达功能性TRAIL-R1和TRAIL-R2。用激动型单抗靶向这些受体可能对EA患者有治疗价值。
The tumour necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/Apo2L) is a member of the TNF superfamily that preferentially induces apoptosis in cancer cells, while sparing normal cells. TRAIL induces apoptosis by interacting with its receptors TRAIL-R1 and TRAIL-R2. Recently, new humanized agonistic anti-TRAIL-R1 and anti-TRAIL-R2 antibodies have been developed, and are undergoing phase I/II clinical trails. Esophageal adenocarcinoma (EA) is associated with significantly poor outcome and is rapidly increasing in incidence in the United States and Western Europe, with virtually no effective non-surgical treatment. The aim of this study was to determine whether human EA tissue express TRAIL-R1 and/or TRAIL-R2, and whether EA cell lines Bic-1 and Seg-1 expresses functional TRAIL-R1 and/or TRAIL-R2. The expression of TRAIL-R1 and TRAIL-R2 was determined in sections from 18 human EA by immunohistochemistry (IHC). Sixteen (89%) of the EA expressed TRAIL-R1 and 17 (94%) expressed TRAIL-R2. Both cell lines were found to express TRAIL-R1 and TRAIL-R2 by western blot analysis, IHC, and flow cytometry. The fully human agonistic TRAIL-R1 (HGS-ETR1) and TRAIL-R2 (HGS-ETR2) antibodies induced apoptosis in Bic-1 and Seg-1 cells in a time and dose dependent manner. Our results show that the vast majority of primary human EA express TRAIL-R1 and TRAIL-R2 and that EA cells lines express functional TRAIL-R1 and TRAIL-R2. Targeting of these receptors by agonist monoclonal antibodies may be of therapeutic value in patients with EA.