TY - JOUR
T1 - Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay
AU - Baccelli, Irène
AU - Schneeweiss, Andreas
AU - Riethdorf, Sabine
AU - Stenzinger, Albrecht
AU - Schillert, Anja
AU - Vogel, Vanessa
AU - Klein, Corinna
AU - Saini, Massimo
AU - Bäuerle, Tobias
AU - Wallwiener, Markus
AU - Holland-Letz, Tim
AU - Höfner, Thomas
AU - Sprick, Martin
AU - Scharpff, Martina
AU - Marmé, Frederik
AU - Sinn, Hans Peter
AU - Pantel, Klaus
AU - Weichert, Wilko
AU - Trumpp, Andreas
N1 - Funding Information:
We thank T. Oskarsson, M. Milsom, H. Medyouf and E. Espinet for helpful discussions, and M. Stoupiec and K. Leotta for technical support, members of the DKFZ FACS core facility, S. Schmitt and K. Hexel for excellent cell sorting, and members of the DKFZ animal facility for animal husbandry. This work was supported by the BioRN Spitzencluster “Molecular and Cell Based Medicine” supported by the German Bundesministerium für Bildung und Forschung, the EU FP7 Program “EuroSyStem”, the Sonderforschungsbereich SFB-873 funded by the Deutsche Forschungsgemeinschaft, the “TIME” consortium Project and the Dietmar Hopp Foundation (all to A.T.) and the European Research Council Advanced Investigator Grant DISSECT (269081 to K.P.).
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84880270290&partnerID=8YFLogxK
U2 - 10.1038/nbt.2576
DO - 10.1038/nbt.2576
M3 - Article
C2 - 23609047
AN - SCOPUS:84880270290
SN - 1087-0156
VL - 31
SP - 539
EP - 544
JO - Nature Biotechnology
JF - Nature Biotechnology
IS - 6
ER -
