Misregulated E-cadherin expression associated with an aggressive brain tumor phenotype.
Misregulated E-cadherin expression associated with an aggressive brain tumor phenotype.
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DOI：
10.1371/journal.pone.0013665
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发表时间：
2010-10-27
期刊：
影响因子：
3.7
通讯作者：
Anastasiadis PZ
中科院分区：
文献类型：
--
作者：
Lewis-Tuffin LJ;Rodriguez F;Giannini C;Scheithauer B;Necela BM;Sarkaria JN;Anastasiadis PZ
钙粘蛋白是介导细胞间粘附和调节细胞运动的粘附连接复合物的重要组成部分。在组织形态发生期间，钙粘蛋白表达的变化（称为钙粘蛋白转换）是改变细胞命运的常见机制。钙粘蛋白转换在上皮肿瘤进展过程中也很常见，认为其促进肿瘤侵袭和转移。E-cadherin是上皮组织中表达最多的钙粘蛋白，但在正常脑组织中的表达非常有限。我们在一系列回顾性的胶质母细胞瘤中发现了上皮或假上皮分化的E-钙粘蛋白表达。与上皮组织不同，神经胶质瘤中的E-钙粘蛋白表达与不利的临床结局相关。两组人GBM细胞系作为裸鼠异种移植物繁殖或在常规细胞培养条件下生长的蛋白质印迹证实E-钙粘蛋白表达是罕见的。然而，少数异种移植系表达E-钙粘蛋白，其表达与细胞原位植入小鼠脑中时增加的侵袭性相关。在常规培养的SF 767神经胶质瘤细胞系中，E-钙粘蛋白表达定位于整个质膜，而不是局限于细胞-细胞接触区域。在这些细胞中E-cadherin的shRNA敲低导致体外增殖和迁移减少。我们的数据显示，GBM肿瘤细胞亚群中E-钙粘蛋白的异常表达与这种侵袭性脑肿瘤亚型的生长和迁移之间存在意想不到的相关性。
Cadherins are essential components of the adherens junction complexes that mediate cell-cell adhesion and regulate cell motility. During tissue morphogenesis, changes in cadherin expression (known as cadherin switching) are a common mechanism for altering cell fate. Cadherin switching is also common during epithelial tumor progression, where it is thought to promote tumor invasion and metastasis. E-cadherin is the predominant cadherin expressed in epithelial tissues, but its expression is very limited in normal brain. We identified E-cadherin expression in a retrospective series of glioblastomas exhibiting epithelial or pseudoepithelial differentiation. Unlike in epithelial tissues, E-cadherin expression in gliomas correlated with an unfavorable clinical outcome. Western blotting of two panels of human GBM cell lines propagated either as xenografts in nude mice or grown under conventional cell culture conditions confirmed that E-cadherin expression is rare. However, a small number of xenograft lines did express E-cadherin, its expression correlating with increased invasiveness when the cells were implanted orthotopically in mouse brain. In the conventionally cultured SF767 glioma cell line, E-cadherin expression was localized throughout the plasma membrane rather than being restricted to areas of cell-cell contact. ShRNA knockdown of E-cadherin in these cells resulted in decreased proliferation and migration in vitro. Our data shows an unexpected correlation between the abnormal expression of E-cadherin in a subset of GBM tumor cells and the growth and migration of this aggressive brain tumor subtype.
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