Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition

被引：2005

作者：

Yu, Min ^{[1
]}

Bardia, Aditya ^{[1
,3
]}

Wittner, Ben S. ^{[1
]}

Stott, Shannon L. ^{[1
,2
]}

Smas, Malgorzata E. ^{[1
]}

Ting, David T. ^{[1
]}

Isakoff, Steven J. ^{[1
,3
]}

Ciciliano, Jordan C. ^{[1
]}

Wells, Marissa N. ^{[1
]}

Shah, Ajay M. ^{[2
]}

Concannon, Kyle F. ^{[1
]}

Donaldson, Maria C. ^{[1
]}

Sequist, Lecia V. ^{[1
,3
]}

Brachtel, Elena ^{[1
,4
]}

Sgroi, Dennis ^{[1
,4
]}

Baselga, Jose ^{[1
,3
]}

Ramaswamy, Sridhar ^{[1
,3
]}

Toner, Mehmet ^{[2
,5
]}

Haber, Daniel A. ^{[1
,3
,6
]}

Maheswaran, Shyamala ^{[1
,5
]}

机构：

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA

[2] Harvard Univ, Sch Med, Ctr Bioengn Med, Charlestown, MA 02129 USA

[3] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA

[4] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA

[5] Harvard Univ, Sch Med, Dept Surg, Charlestown, MA 02129 USA

[6] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

SCIENCE | 2013年 / 339卷 / 6119期

关键词：

TRANSITION; EMT; DISSEMINATION; METASTASIS;

D O I：

10.1126/science.1228522

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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)-beta pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.

引用

页码：580 / 584

页数：5

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