Expression of TRAIL (TNF-related apoptosis-inducing ligand) and its receptors in normal colonic mucosa, adenomas, and carcinomas
Expression of TRAIL (TNF-related apoptosis-inducing ligand) and its receptors in normal colonic mucosa, adenomas, and carcinomas
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DOI：
10.1002/path.1364
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发表时间：
2003-07-01
影响因子：
7.3
通讯作者：
de Jong, S
中科院分区：
文献类型：
--
作者：
Koornstra, JJ;Kleibeuker, JH;de Jong, S
肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导肿瘤细胞凋亡已经鉴定了TRAIL的四种膜结合受体，两种凋亡介导受体DR 4和DR 5，以及两种凋亡抑制受体DcR 1和DcR 2。本研究的目的是研究TRAIL及其受体在结直肠癌发展中的作用。采用免疫组化方法检测10例正常粘膜、19例腺瘤和21例癌组织中TRAIL及其受体的表达和定位。探讨肿瘤坏死因子相关凋亡配体（TRAIL）及其受体表达与肿瘤细胞凋亡程度（M30表达）及组织病理学特征的关系。TRAIL及其受体在正常粘膜上皮中表达。受体的表达被认为是在腺瘤和癌。在结直肠肿瘤的一个亚组中，TRAIL表达丢失，在癌中比在腺瘤中更常见（p < 0.05）。肿瘤细胞中DR 4和DR 5染色比正常细胞更强，并伴有更高程度的细胞凋亡。DcR 1和DcR 2的表达在肿瘤细胞和正常细胞之间没有差异。TRAIL及其受体表达与组织病理学特征无相关性。总之，在腺瘤-癌序列的过程中观察到TRAIL和TRAIL受体DR 4和DR 5的表达的显著变化。DR 4和DR 5在肿瘤细胞中的表达比在正常细胞中的表达更强，以及更高程度的细胞凋亡，表明这些受体在肿瘤性结直肠细胞中诱导细胞凋亡中可能具有功能作用。版权所有（C）2003约翰威利父子有限公司。
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis intumour cell lines. Four membrane-bound receptors for TRAIL have been identified, two apoptosis-mediating receptors, DR4 and DR5, and two apoptosis-inhibiting receptors, DcR1 and DcR2. The aim of this study was to examine the role of TRAIL and its receptors in colorectal cancer development. The immunohistochemical expression and localization of TRAIL and its receptors were investigated in normal mucosa (n = 10), adenomas (n = 19), and carcinomas (n = 21). Correlations between the expression of TRAIL and its receptors and the degree of apoptosis (assessed by M30 expression) and histopathological characteristics were explored. TRAIL and its receptors were expressed in normal mucosal epithelium. Expression of the receptors was seen in adenomas and carcinomas. TRAIL expression was lost in a subset of colorectal tumours, more frequently in carcinomas than in adenomas (p < 0.05). DR4 and DR5 staining was stronger in neoplastic cells than in normal cells and was accompanied by a higher degree of apoptosis. No differences were found between tumour and normal cells regarding DcR1 and DcR2 expression. No correlations were found between TRAIL or TRAIL receptor expression and histopathological characteristics. In conclusion, marked changes were seen in the course of the adenoma-carcinoma sequence with respect to the expression of TRAIL and TRAIL receptors DR4 and DR5. The stronger expression of DR4 and DR5 in neoplastic cells than in normal cells, together with a higher degree of apoptosis, suggests a possible functional role for these receptors in apoptosis induction in neoplastic colorectal cells. Copyright (C) 2003 John Wiley Sons, Ltd.