Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay

被引：833

作者：

Baccelli, Irene ^{[1
,2
]}

Schneeweiss, Andreas ^{[3
]}

Riethdorf, Sabine ^{[4
]}

Stenzinger, Albrecht ^{[5
]}

Schillert, Anja ^{[1
,2
]}

Vogel, Vanessa ^{[1
,2
,5
]}

Klein, Corinna ^{[1
,2
]}

Saini, Massimo ^{[1
]}

Baeuerle, Tobias ^{[6
]}

Wallwiener, Markus ^{[3
]}

Holland-Letz, Tim ^{[7
]}

Hoefner, Thomas ^{[1
,2
]}

Sprick, Martin ^{[1
,2
]}

Scharpff, Martina ^{[3
]}

Marme, Frederik ^{[3
]}

Sinn, Hans Peter ^{[5
]}

Pantel, Klaus ^{[4
]}

Weichert, Wilko ^{[5
]}

Trumpp, Andreas ^{[1
,2
,8
]}

机构：

[1] Heidelberg Inst Stem Cell Technol & Expt Med gGmb, Heidelberg, Germany

[2] Deutsch Krebsforschungszentrum DKFZ, Div Stem Cells & Canc, Heidelberg, Germany

[3] Univ Heidelberg Hosp, Natl Ctr Tumor Dis, Heidelberg, Germany

[4] Univ Klinikum Hamburg Eppendorf, Dept Tumor Biol, Hamburg, Germany

[5] Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany

[6] DKFZ, Dept Med Phys Radiol, Heidelberg, Germany

[7] DKFZ, Dept Biostat, Heidelberg, Germany

[8] German Canc Consortium, Heidelberg, Germany

来源：

NATURE BIOTECHNOLOGY | 2013年 / 31卷 / 06期

基金：

欧洲研究理事会;

关键词：

PROGNOSTIC-SIGNIFICANCE; THERAPEUTIC TARGET; PERIPHERAL-BLOOD; BONE-MARROW; STEM-CELLS; EXPRESSION; SURVIVAL; CD47; MET; DISSEMINATION;

D O I：

10.1038/nbt.2576

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

It has been hypothesized that carcinoma metastasis is initiated by a subpopulation of circulating tumor cells (CTCs) found in the blood of patients. However, although the presence of CTCs is an indicator of poor prognosis in several carcinoma entities, the existence and phenotype of metastasis-initiating cells (MICs) among CTCs has not been experimentally demonstrated. Here we developed a xenograft assay and used it to show that primary human luminal breast cancer CTCs contain MICs that give rise to bone, lung and liver metastases in mice. These MIC-containing CTC populations expressed EPCAM, CD44, CD47 and MET. In a small cohort of patients with metastases, the number of EPCAM(+)CD44(+)CD47(+)MET(+) CTCs, but not of bulk EPCAM(+) CTCs, correlated with lower overall survival and increased number of metastasic sites. These data describe functional circulating MICs and associated markers, which may aid the design of better tools to diagnose and treat metastatic breast cancer.

引用

页码：539 / U143

页数：7

共 43 条

[41] The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors [J].

Willingham, Stephen B. ;

Volkmer, Jens-Peter ;

Gentles, Andrew J. ;

Sahoo, Debashis ;

Dalerba, Piero ;

Mitra, Siddhartha S. ;

Wang, Jian ;

Contreras-Trujillo, Humberto ;

Martin, Robin ;

Cohen, Justin D. ;

Lovelace, Patricia ;

Scheeren, Ferenc A. ;

Chao, Mark P. ;

Weiskopf, Kipp ;

Tang, Chad ;

Volkmer, Anne Kathrin ;

Naik, Tejaswitha J. ;

Storm, Theresa A. ;

Mosley, Adriane R. ;

Edris, Badreddin ;

Schmid, Seraina M. ;

Sun, Chris K. ;

Chua, Mei-Sze ;

Murillo, Oihana ;

Rajendran, Pradeep ;

Cha, Adriel C. ;

Chin, Robert K. ;

Kim, Dongkyoon ;

Adorno, Maddalena ;

Raveh, Tal ;

Tseng, Diane ;

Jaiswal, Siddhartha ;

Enger, Per Oyvind ;

Steinberg, Gary K. ;

Li, Gordon ;

So, Samuel K. ;

Majeti, Ravindra ;

Harsh, Griffith R. ;

van de Rijn, Matt ;

Teng, Nelson N. H. ;

Sunwoo, John B. ;

Alizadeh, Ash A. ;

Clarke, Michael F. ;

Weissman, Irving L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (17) :6662-6667

[42] Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition [J].

Yu, Min ;

Bardia, Aditya ;

Wittner, Ben S. ;

Stott, Shannon L. ;

Smas, Malgorzata E. ;

Ting, David T. ;

Isakoff, Steven J. ;

Ciciliano, Jordan C. ;

Wells, Marissa N. ;

Shah, Ajay M. ;

Concannon, Kyle F. ;

Donaldson, Maria C. ;

Sequist, Lecia V. ;

Brachtel, Elena ;

Sgroi, Dennis ;

Baselga, Jose ;

Ramaswamy, Sridhar ;

Toner, Mehmet ;

Haber, Daniel A. ;

Maheswaran, Shyamala .

SCIENCE, 2013, 339 (6119) :580-584

[43] Circulating tumor cells: approaches to isolation and characterization [J].

Yu, Min ;

Stott, Shannon ;

Toner, Mehmet ;

Maheswaran, Shyamala ;

Haber, Daniel A. .

JOURNAL OF CELL BIOLOGY, 2011, 192 (03) :373-382

← 1 2 3 4 5 →