Epithelial-to-mesenchytnal transition and stem cells in endometrial cancer
Epithelial-to-mesenchytnal transition and stem cells in endometrial cancer
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DOI：
10.1016/j.humpath.2013.04.009
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发表时间：
2013-10-01
期刊：
影响因子：
3.3
通讯作者：
Matias-Guiu, Xavier
中科院分区：
文献类型：
--
作者：
Mirantes, Cristina;Espinosa, Inigo;Matias-Guiu, Xavier
本文综述了上皮间质转化（EMT）的主要特征及其在了解子宫内膜癌（EC）肌层浸润以及恶性苗勒管混合瘤（MMMT）发展中的可能作用。此外，本文还讨论了体细胞（SSC）和癌症干细胞（CSC）在EC中的可能作用。在EMT中已经鉴定了E-cadherin的不同转录抑制因子，包括Snail和Slug、ZEB 1和ZEB 2以及E47和Twist。其中一些基因的表达在肌浸润前沿增加，并与E-钙粘蛋白免疫反应性呈负相关。而EMT现象的短暂发生是重要的肌层浸润在传统的EC，MMMT显示永久性表达EMT导致E-钙粘蛋白的抑制和间充质标记物的表达增加，包括蛋白质参与骨骼肌发育。通过Hoechst染料排除试验评估，在人子宫内膜中发现了SSC群体，确定为侧群。CSC已被定义为与SSC类似的具有自我更新能力的癌细胞，这意味着经历允许产生更相同的CSC并产生恶性肿瘤中发现的多种更分化的细胞的分裂。虽然已发表的数据显示CD 133（+）细胞保留了CSC的特征，但没有确凿的证据表明CD 133是EC干细胞的通用标志物。最后，对子宫内膜干细胞在卵巢子宫内膜异位症和卵巢类囊腺癌发生发展中的可能作用进行了评论。(C)2013 Elsevier Inc. All rights reserved.
This review article describes the main features of epithelial-to-mesenchymal transition (EMT) and its possible role in understanding myometrial invasion in endometrial carcinoma (EC), as well as the development of malignant mixed Mullerian tumor (MMMT). Moreover, the article discusses the possible role of somatic (SSC) and cancer stem cells (CSC) in EC. Different transcriptional repressors of E-cadherin have been identified in EMT, including Snail and Slug, ZEB1 and ZEB2, and E47 and Twist. The expression of some of these genes is increased at the myoinvasive front and correlates inversely with E-cadherin inmunoreactivity. Whereas the transient occurrence of the EMT phenomenon is important for myometrial invasion in conventional EC, MMMT shows permanent expression of EMT leading to repression of E-cadherin and increased expression of mesenchymal markers including proteins involved in skeletal muscle development. An SSC population, identified as a side population, assessed by the Hoechst dye exclusion test has been identified in human endometrium. CSCs have been defined in analogy to SSC as cancer cells that have the capacity to self-renew, which means undergoing divisions that allow the generation of more identical CSCs and give rise to the variety of more differentiated cells found in the malignancy. Although published data show that CD133(+) cells retain the characteristics of CSC, there is no conclusive evidence showing that CD133 is the universal marker for EC stem cells. Finally, a possible role for endometrial stem cells in the development of ovarian endometriosis and ovarian endometrioid carcinoma is commented. (C) 2013 Elsevier Inc. All rights reserved.