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上皮-间质转化:在脑膜瘤中的可能作用

Epithelial-to-mesenchymal transition: possible role in meningiomas.

作者信息

Pecina-Slaus Nives, Cicvara-Pecina Tatjana, Kafka Anja

机构信息

Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Salata 12, HR-10000 Zagreb, Croatia.

出版信息

Front Biosci (Elite Ed). 2012 Jan 1;4(3):889-96. doi: 10.2741/E427.

Abstract

Epithelial-to-mesenchimal transition (EMT) is a process involved in invasion and metastasis of tumors. The occurrence of EMT during tumor progression resembles the developmental scenario and sheds light on important mechanisms for the initial step of metastasis - invasion where noninvasive tumor cells acquire motility and ultimately disseminate to distant organs. The hallmark of EMT is the loss of expression of the cell-cell adhesion molecule E-cadherin. The numerous reports by many authors as well as our own results indicate that E-cadherin plays a role in CNS tumors - meningiomas. Our studies showed that 73 % of meningiomas had downregulation of E-cadherin. Moreover, loss of heterozygosity of E-cadherin was observed in 32 % of meningiomas. Bound to E-cadherin in adherens junctions is beta-catenin, whose translocation to the nucleus is yet another molecular event involved in EMT. In our study beta-catenin was progressively upregulated from meningothelial to atypical, while 60 % of anaplastic meningiomas showed upregulation and nuclear localization of the protein. The elucidation of molecular mechanisms that govern EMT will offer new approaches and targets to restrain metastasis.

摘要

上皮-间质转化(EMT)是一个参与肿瘤侵袭和转移的过程。肿瘤进展过程中EMT的发生类似于发育过程,为转移起始步骤——侵袭的重要机制提供了线索,在侵袭过程中,非侵袭性肿瘤细胞获得运动能力并最终扩散到远处器官。EMT的标志是细胞间粘附分子E-钙粘蛋白表达的丧失。许多作者的大量报道以及我们自己的研究结果表明,E-钙粘蛋白在中枢神经系统肿瘤——脑膜瘤中发挥作用。我们的研究表明,73%的脑膜瘤存在E-钙粘蛋白下调。此外,在32%的脑膜瘤中观察到E-钙粘蛋白杂合性缺失。与E-钙粘蛋白结合在黏着连接处的是β-连环蛋白,其向细胞核的易位是另一个参与EMT的分子事件。在我们的研究中,β-连环蛋白从脑膜皮型到非典型型逐渐上调,而60%的间变性脑膜瘤显示该蛋白上调并定位于细胞核。对控制EMT的分子机制的阐明将为抑制转移提供新的方法和靶点。

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