The role of trophinin, an adhesion molecule unique to human trophoblasts, in progression of colorectal cancer
The role of trophinin, an adhesion molecule unique to human trophoblasts, in progression of colorectal cancer
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DOI：
10.1002/ijc.22821
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发表时间：
2007-09-01
影响因子：
6.4
通讯作者：
Nakayama, Jun
中科院分区：
文献类型：
--
作者：
Harada, Oi;Suga, Tomoaki;Nakayama, Jun
Trophinin是由人滋养层细胞表达的一种独特的粘附分子。其活性和体内表达模式暗示滋养层蛋白在滋养外胚层细胞与母体上皮细胞的初始附着中起作用。在顶端粘附之后，滋养层细胞侵袭母体组织形成胎盘，这一过程类似于肿瘤侵袭。在这里，我们报告说，trophinin表达的肿瘤从64%的结肠癌患者（n = 50）和高trophinin表达与预后不良密切相关。为了确定营养素表达和恶性肿瘤之间的联系，结肠腺癌SW 480细胞稳定转染营养素。侵袭实验表明，表达trophinin的SW 480细胞比模拟转染的细胞更具侵袭性。微阵列分析比较转染滋养蛋白与模拟转染细胞的SW 480细胞，确定高迁移率族蛋白1（HMGB 1）作为最显着升高的转录。结直肠癌患者肿瘤的免疫组化分析证实了HMGB 1蛋白在细胞核中的表达与肿瘤中营养素的表达呈正相关。HMGB 1和其配体β 1（晚期糖基化终产物受体）蛋白在65.6%的营养素阳性患者（n = 32）中共表达。这些结果表明，营养素通过涉及HMGB 1/HMGB 2的机制促进侵袭。(C)2007 Wiley-Liss，Inc.
Trophinin is a unique adhesion molecule expressed by human trophoblastic cells. Its activity and in vivo expression pattern implicate trophinin in the initial attachment of trophectoderm cells to maternal epithelia. Subsequent to apical adhesion, trophoblasts aggressively invade maternal tissue to form the placenta, a process resembling tumor invasion. Here, we report that trophinin is expressed in tumors from 64% of colon cancer patients (n = 50) and high trophinin expression is closely associated with poor prognosis. To determine the link between trophinin expression and malignancy, colon adenocarcinoma SW480 cells were stably transfected with trophinin. An invasion assay showed that trophininexpressing SW480 cells were more invasive than mock-transfected cells. Microarray analysis comparing SW480 cells transfected with trophinin with mock-transfected cells identified high-mobility group box 1 (HMGB1) as the most significantly elevated transcript. Immunohistochemical analysis of tumors from the colorectal cancer patients confirmed positive correlation of HMGB1 protein expression in the nucleus to trophinin expression in tumor. HMGB1 and its ligand RAGE (the receptor for advanced glycation end product) proteins were coexpressed in 65.6% of trophinin-positive patients (n = 32). These results suggest that trophinin promotes invasion through a mechanism involving HMGB1/ RAGE. (C) 2007 Wiley-Liss, Inc.