来自美国哈佛医学院的研究人员发现在乳腺癌病人血液中循环运输的肿瘤细胞——循环肿瘤细胞(CTCs)经历的表型变化——上皮细胞与间充质细胞的组成比例变化可能促进了循环肿瘤细胞的扩散。这项研究确定的潜在机制或将成为癌症的潜在治疗靶标。

-2013年2月1日《科学》


中文翻译


【题目】漫游乳腺癌细胞变形记

【译文】贴壁的上皮细胞经过上皮细胞-间充质细胞转化(EMT),可转变为可迁移的间充质状态。在临床前期模型中,这一过程参与了肿瘤转移。为了研究它在人类癌症中的作用,本研究描述了乳腺癌患者体内循环肿瘤细胞(CTCs)中的上皮细胞-间充质细胞转化的特点。原发肿瘤细胞很少同时表达间充质标记物和上皮标记物,但是循环肿瘤细胞中含有大量的间充质细胞。对11例病人的循环肿瘤细胞的连续监测表明间充质细胞在循环肿瘤细胞中的组成与癌症发展有关。在癌症治疗与癌症发展的每个循环过程中,病人体内这些细胞的命运相应地发生可逆性转变。间充质细胞组成的CTCs均可以单细胞和多细胞簇的形式出现,同时表达已知的EMT调节因子,包括转化生长因子(TGF)–β信号通路组分和FOXC1转录因子。这些发现证实EMT在人类乳腺癌的血液播散中起到了一定作用。

英文原稿


[Title]: Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition

[Authors]: Min Yu, Aditya Bardia, Ben S. Wittner, Shannon L. Stott, Malgorzata E. Smas, David T. Ting, Steven J. Isakoff, Jordan C. Ciciliano, Marissa N. Wells, Ajay M. Shah, Kyle F. Concannon, Maria C. Donaldson, Lecia V. Sequist, Elena Brachtel, Dennis Sgroi, Jose Baselga, Sridhar Ramaswamy, Mehmet Toner, Daniel A. Haber, and Shyamala Maheswaran

[Abstract]: Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)–β pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.

原文地址

 http://www.sciencemag.org/content/339/6119/580.short

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