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Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells

qinkunhua 添加于 2011-9-28 16:21 | 953 次阅读 | 0 个评论

作者
Sullivan NJ, Sasser AK, Axel AE, Vesuna F, Raman V, Ramirez N, Oberyszyn TM, Hall BM
摘要
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-alpha-positive human breast cancer cells. Furthermore, ectopic stable IL-6 expressing MCF-7 breast adenocarcinoma cells (MCF-7(IL-6)) exhibited an EMT phenotype characterized by impaired E-cadherin expression and induction of Vimentin, N-cadherin, Snail and Twist. MCF-7(IL-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.
详细资料
- 文献种类:期刊
- 期刊名称: Oncogene
- 期刊缩写: Oncogene
- 期卷页: 2009年第28卷第33期 2940-2947页
- 地址: Integrated Biomedical Science Graduate Program, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
- ISBN: 0950-9232
- 备注:PMID:19581928
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附件
Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human br