Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype
Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype
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DOI：
10.1158/0008-5472.can-07-2017
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发表时间：
2008-02-15
期刊：
影响因子：
11.2
通讯作者：
Palacios, José
中科院分区：
文献类型：
--
作者：
Sarrió, David;Rodriguez-Pinilla, Socorro Maria;Palacios, José
上皮-间质转化（EMT）的定义是上皮特征的丧失和间质表型的获得。在癌细胞中，EMT 可能与侵袭性、侵袭性和转移潜力的增加有关。为了评估人类乳腺肿瘤中 EMT 的发生，我们使用 28 种不同的标记物对 479 例浸润性乳腺癌和 12 例癌肉瘤进行了基于组织微阵列的免疫组织化学研究。肿瘤的无监督分层聚类和统计分析表明，EMT 标记物（波形蛋白、平滑肌肌动蛋白、N-钙粘蛋白和钙粘蛋白-11）上调，参与细胞外基质重塑和侵袭的蛋白质（SPARC、层粘连蛋白和肌成束蛋白）过度表达，同时特征性上皮标记物（E-钙粘蛋白和肌成束蛋白）减少。 细胞角蛋白），优先发生在具有“基底样表型”的乳腺肿瘤中。此外，大多数乳腺癌肉瘤也具有基底样表型，并在其肉瘤和上皮成分中显示间充质标志物的表达。为了评估基底样细胞是否具有间质转化的内在表型可塑性，我们用 MCF10A 细胞系进行了体外研究。为了应对低细胞密度，MCF10A 细胞会发生自发的形态和表型 EMT 样变化，包括细胞骨架重组、波形蛋白和 Slug 上调、钙粘蛋白转换以及连环蛋白的弥漫性胞质重新定位。此外，这些表型变化与 EMT 过程的整体遗传分化程序特征的修改有关。总之，我们的数据表明，在乳腺肿瘤中，EMT 可能发生在特定的遗传背景（基础表型）内，并表明这种间质转化的倾向可能与这些肿瘤的高侵袭性和特征性转移扩散有关。
Epithelial-mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. In carcinoma cells, EMT can be associated with increased aggressiveness, and invasive and metastatic potential. To assess the occurrence of EMT in human breast tumors, we conducted a tissue microarray-based immunohistochemical study in 479 invasive breast carcinomas and 12 carcinosarcomas using 28 different markers. Unsupervised hierarchical clustering of the tumors and statistical analysis showed that up-regulation of EMT markers (vimentin, smooth-muscle-actin, N-cadherin, and cadherin-11) and overexpression of proteins involved in extracellular matrix remodeling and invasion (SPARC, laminin, and fascin), together with reduction of characteristic epithelial markers (E-cadherin and cytokeratins), preferentially occur in breast tumors with the "basal-like phenotype." Moreover, most breast carcinosarcomas also had a basal-like phenotype and showed expression of mesenchymal markers in their sarcomatous and epithelial components. To assess whether basal-like cells have intrinsic phenotypic plasticity for mesenchyrnal transition, we performed in vitro studies with the MCF10A cell line. In response to low cell density, MCF10A cells suffer spontaneous morphologic and phenotypic EMT-like changes, including cytoskeleton reorganization, vimentin and Slug up-regulation, cadherin switching, and diffuse cytosolic relocalization of the catenins. Moreover, these phenotypic changes are associated with modifications in the global genetic differentiation program characteristic of the EMT process. In summary, our data indicate that in breast tumors, EMT likely occurs within a specific genetic context, the basal phenotype, and suggests that this proclivity to mesenchymal transition may be related to the high aggressiveness and the characteristic metastatic spread of these tumors.