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首页> 外文期刊>Expert opinion on therapeutic targets >Expression of Cox-2 in human breast cancer cells as a critical determinant of epithelial-to-mesenchymal transition and invasiveness
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Expression of Cox-2 in human breast cancer cells as a critical determinant of epithelial-to-mesenchymal transition and invasiveness

机译：Cox-2在人乳腺癌细胞中的表达是上皮-间质转化和侵袭性的关键决定因素

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Introduction: Cyclooxygenase-2 (COX-2) is overexpressed in several malignancies and is implicated in breast cancer progression. Objectives: We investigated whether changes in COX-2 expression may affect epithelial-to- mesenchymal transition (EMT) and then invasive potential of human breast cancer cells, in relationship with hypoxia. COX-2-null MCF-7 human breast cancer cells, MCF-7 cells transiently expressing COX-2 and COX-2-expressing MDA-MB-231 cells were employed. Results: COX-2 overexpression resulted in downregulation of E-cadherin and β-catenin, upregulation of vimentin, N-cadherin and SNAI1, suggesting EMT occurrence. COX-2-overexpressing MCF-7 cells were also characterized by increased invasiveness and release of matrix-metalloproteinase- 9. The above-mentioned characteristics, homologous to those detected in highly invasive MDA-MB-231 cells, were reverted by treatment of COX-2-overexpressing MCF-7 cells with celecoxib, a COX-2-specific inhibitor, partly through the inhibition of COX-2-related intracellular generation of reactive oxygen species. Hypoxia further exacerbated COX-2 expression, EMT changes and invasive ability in both COX-2-overexpressing MCF-7 cells and MDA-MB-231 cells. Finally, immunohistochemistry performed on samples from normal and neoplastic human breast tissues revealed that COX-2-positive malignant cells were also positive for EMT-related antigens, hypoxia-inducible factor (HIF)-2α and the oxidative stress marker heme oxygenase. Conclusions: These findings support the existence of a direct link between COX-2 overexpression, EMT and invasiveness in human breast cancer cells, emphasizing the role of hypoxic microenvironment.
机译：简介：环氧合酶2（COX-2）在几种恶性肿瘤中过表达，并与乳腺癌的进展有关。目的：我们研究了COX-2表达的变化是否会影响缺氧与人乳腺癌细胞的上皮-间充质转化（EMT）以及侵袭潜能有关。使用了COX-2-无效的MCF-7人乳腺癌细胞，瞬时表达COX-2的MCF-7细胞和表达COX-2的MDA-MB-231细胞。结果：COX-2过表达导致E-钙粘蛋白和β-连环蛋白下调，波形蛋白，N-钙粘蛋白和SNAI1上调，提示EMT的发生。 COX-2过表达的MCF-7细胞的特征还在于增加的侵袭性和基质金属蛋白酶9的释放。上述特征与高侵害性MDA-MB-231细胞中检测到的特征同源，通过治疗COX得以恢复塞来昔布（一种COX-2特异性抑制剂）-2-过度表达MCF-7细胞，部分是通过抑制COX-2相关的细胞内活性氧的生成来实现的。缺氧进一步加剧了COX-2过表达的MCF-7细胞和MDA-MB-231细胞中COX-2的表达，EMT的变化和侵袭能力。最后，对来自正常和赘生性人类乳腺组织的样本进行的免疫组织化学分析显示，COX-2阳性恶性细胞也对EMT相关抗原，缺氧诱导因子（HIF）-2α和氧化应激标记血红素加氧酶呈阳性。结论：这些发现支持COX-2过表达，EMT与人乳腺癌细胞侵袭性之间存在直接联系，强调了低氧微环境的作用。

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