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源自巴雷特食管的食管腺癌中的上皮-间质转化与癌症干细胞

Epithelial mesenchymal transition and cancer stem cells in esophageal adenocarcinoma originating from Barrett's esophagus.

作者信息

Tomizawa Yutaka, Wu Tsung-Teh, Wang Kenneth K

机构信息

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

出版信息

Oncol Lett. 2012 May;3(5):1059-1063. doi: 10.3892/ol.2012.632. Epub 2012 Mar 5.

Abstract

Carcinomas comprise cohesive epithelial cells linked to one another by E-cadherin-based cell-cell junctions. Epithelial mesenchymal transition (EMT) enables carcinoma cells to migrate from the original tissue and invade into stromal components. The E-cadherin promoter is frequently repressed by specific transcriptional repressors including Snail, Slug and Twist. CD133 is known to be a marker of tumor-initiating cells in human cancers. This is the first study to characterize the transcriptional factors for E-cadherin and the representative cancer stem cell marker in specimens of early esophageal adenocarcinoma (EAC) originating from Barrett's esophagus. Ten surgically treated patients were analyzed in the present study. Immunohistochemistry was performed to determine the expression of Snail, Slug, Twist and CD133, and the results were scored. Unlike previous studies of advanced stage esophageal cancers showing the overexpression of each specific transcriptional protein, the invading edges of the tumor were found to abundantly express Snail, Slug, Twist and CD133 in our cohort. Therefore, results of this study suggest that early stage cancers predominantly comprise cells with metastatic potential and this evidence adds legitimacy to the complete removal of early EAC.

摘要

癌组织由通过基于E-钙黏蛋白的细胞间连接相互连接的黏附上皮细胞组成。上皮-间质转化(EMT)使癌细胞能够从原始组织迁移并侵入基质成分。E-钙黏蛋白启动子经常被包括Snail、Slug和Twist在内的特定转录抑制因子所抑制。已知CD133是人类癌症中肿瘤起始细胞的标志物。这是第一项对源自巴雷特食管的早期食管腺癌(EAC)标本中E-钙黏蛋白的转录因子和代表性癌症干细胞标志物进行表征的研究。本研究分析了10例接受手术治疗的患者。进行免疫组织化学以确定Snail、Slug、Twist和CD133的表达,并对结果进行评分。与先前关于晚期食管癌显示每种特定转录蛋白过表达的研究不同,在我们的队列中发现肿瘤的侵袭边缘大量表达Snail、Slug、Twist和CD133。因此,本研究结果表明早期癌症主要由具有转移潜能的细胞组成,这一证据为早期EAC的彻底切除增加了合理性。

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