Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay
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Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. / Baccelli, Irène; Schneeweiss, Andreas; Riethdorf, Sabine; Stenzinger, Albrecht; Schillert, Anja; Vogel, Vanessa; Klein, Corinna; Saini, Massimo; Bäuerle, Tobias; Wallwiener, Markus; Holland-Letz, Tim; Höfner, Thomas; Sprick, Martin; Scharpff, Martina; Marmé, Frederik; Sinn, Hans Peter; Pantel, Klaus; Weichert, Wilko; Trumpp, Andreas.
in: NAT BIOTECHNOL, Jahrgang 31, Nr. 6, 01.06.2013, S. 539-44.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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
PY - 2013/6/1
Y1 - 2013/6/1
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.
KW - Adult
KW - Aged
KW - Animals
KW - Breast Neoplasms
KW - Cell Count
KW - Cell Line, Tumor
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Mice
KW - Middle Aged
KW - Neoplasm Metastasis
KW - Neoplastic Cells, Circulating
KW - Prognosis
KW - Tumor Markers, Biological
KW - Xenograft Model Antitumor Assays
U2 - 10.1038/nbt.2576
DO - 10.1038/nbt.2576
M3 - SCORING: Journal article
C2 - 23609047
VL - 31
SP - 539
EP - 544
JO - NAT BIOTECHNOL
JF - NAT BIOTECHNOL
SN - 1087-0156
IS - 6
ER -