Repressed E-cadherin expression in the lower crypt of human small intestine:: a cell marker of functional relevance
Repressed E-cadherin expression in the lower crypt of human small intestine:: a cell marker of functional relevance
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DOI：
10.1016/j.yexcr.2004.08.033
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发表时间：
2005-01-15
影响因子：
3.7
通讯作者：
Beaulieu, JF
中科院分区：
文献类型：
--
作者：
Escaffit, F;Perreault, N;Beaulieu, JF
在上皮细胞中，E-钙粘附素的异常表达与细胞极化和/或分化的丧失有关。然而，最近的观察表明，E-钙粘附素在生理条件下也可以被抑制，例如在一些上皮干细胞系中。在目前的工作中，我们分析了E-钙粘蛋白在人类肠上皮细胞前体细胞中的表达，并探讨了其潜在的作用。用免疫荧光法检测小肠冰冻切片上E-钙粘附素在隐窝绒毛轴上的表达。研究发现，E-钙粘附素在隐窝底部的细胞中有不同程度的表达，表达明显减弱。令人惊讶的是，在我们实验室分离的正常人类肠上皮(HIEC)隐窝细胞模型中，既没有检测到E-钙粘素蛋白，也没有检测到E-钙粘素转录本，而其他与E-钙粘附素相关的成分，如连环蛋白和APC，都存在。在HIEC细胞中，E-钙粘附素的强制表达增加了膜相关的β-连环素，并伴随着细胞-细胞界面连接样结构的出现。在功能上，与对照组相比，表达E-钙粘素的HIEC细胞的细胞动力学和p21(Cip)水平发生了变化。此外，还观察到迁移能力显著降低，对失巢凋亡的敏感性增加。这些结果表明，E-钙粘附素的下调表达是人类肠道隐窝基础细胞相关的特征，似乎与维持祖细胞种群具有功能相关性。(C)2004 Elsevier Inc.保留所有权利。
In epithelia, abnormal expression of E-cadherin is related to pathologies involving a loss of cell polarization and/or differentiation. However, recent observations suggest that E-cadherin could also be repressed under physiological conditions, such as in some epithelial stem cell lineages. In the present work, we have analyzed E-cadherin expression in human intestinal epithelial cell progenitors and investigated its potential role. E-cadherin expression was analyzed along the crypt-villus axis by immunofluorescence on cryosections of small intestine. E-cadherin was found to be differentially expressed, being significantly weaker in the cells located at the bottom of the crypts. Surprisingly, neither the E-cadherin protein nor transcript were detected in a normal human intestinal epithelial (HIEC) crypt cell model isolated in our laboratory, whereas other E-cadherin-related components such as catenins and APC were present. Forced expression of E-cadherin in HIEC cells increased membrane-associated beta-catenin and was accompanied by the appearance of junction-like structures at the cell-cell interface. Functionally, cell kinetics and p21(Cip) levels were found to be altered in the E-cadherin expressing HIEC cells as compared to controls. Furthermore, a significant reduction of the migration abilities and an increase in sensitivity to anoikis were also observed. These results suggest that down-regulated expression of E-cadherin is a human intestinal crypt base cell-related feature that appears to be of functional relevance for the maintenance of the progenitor cell population. (C) 2004 Elsevier Inc. All rights reserved.