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首页> 外文期刊>Oncogene >Interleukin-6 induces an epithelial|[ndash]|mesenchymal transition phenotype in human breast cancer cells
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Interleukin-6 induces an epithelial|[ndash]|mesenchymal transition phenotype in human breast cancer cells

机译:白细胞介素6诱导人乳腺癌细胞上皮|间充质转化表型

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Breast tumor interleukin-6 (IL-6) levels increase with tumor grade, and elevated serum IL-6 correlates with poor breast cancer patient survival. Epithelial–mesenchymal transition (EMT) phenotypes such as impaired E-cadherin expression or aberrant Vimentin induction are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Despite this fact, few tumor microenvironment-derived extracellular signaling factors capable of provoking such a phenotypic transition have been identified. In this study, we showed that IL-6 promoted E-cadherin repression among a panel of estrogen receptor-α-positive human breast cancer cells. Furthermore, ectopic stable IL-6 expressing MCF-7 breast adenocarcinoma cells (MCF-7IL?6) exhibited an EMT phenotype characterized by impaired E-cadherin expression and induction of Vimentin, N-cadherin, Snail and Twist. MCF-7IL?6 cells formed xenograft tumors that displayed loss of E-cadherin, robust Vimentin induction, increased proliferative indices, advanced tumor grade and undifferentiated histology. Finally, we showed aberrant IL-6 production and STAT3 activation in MCF-7 cells that constitutively express Twist, a metastatic regulator and direct transcriptional repressor of E-cadherin. To our knowledge, this is the first study that shows IL-6 as an inducer of an EMT phenotype in breast cancer cells and implicates its potential to promote breast cancer metastasis.
机译:乳腺癌白细胞介素6(IL-6)的水平随肿瘤等级而增加,血清IL-6升高与乳腺癌患者的不良生存相关。上皮-间质转化(EMT)表型,如E-钙粘蛋白表达受损或波形蛋白诱导异常,与乳腺癌的转移增加和临床预后不良有关。尽管有这个事实,但几乎没有发现能够引起这种表型转变的肿瘤微环境来源的细胞外信号转导因子。在这项研究中,我们表明IL-6可以促进一组雌激素受体-α阳性人乳腺癌细胞中的E-钙粘着蛋白抑制。此外,异位稳定表达IL-6的MCF-7乳腺腺癌细胞(MCF-7IL?6)表现出EMT表型,其特征是E-钙粘蛋白表达受损以及波形蛋白,N-钙粘蛋白,蜗牛和扭曲的诱导。 MCF-7IL?6细胞形成异种移植肿瘤,表现出E-钙黏着蛋白损失,强劲的波形蛋白诱导,增生指数增加,肿瘤分级升高和组织学未分化。最后,我们在组成性表达Twist的MCF-7细胞中显示了异常的IL-6产生和STAT3激活,Twist是一种转移性调节剂,直接表达E-钙粘蛋白。据我们所知,这是第一项显示IL-6作为乳腺癌细胞EMT表型的诱导剂并暗示其促进乳腺癌转移的潜力的研究。

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