title: Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay.
abstract: 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.
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH, Heidelberg, Germany.
authors.forename: Irène
authors.initials: I
authors.lastname: Baccelli
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stenzinger
authors.forename: Anja
authors.initials: A
authors.lastname: Schillert
authors.forename: Vanessa
authors.initials: V
authors.lastname: Vogel
authors.forename: Corinna
authors.initials: C
authors.lastname: Klein
authors.forename: Massimo
authors.initials: M
authors.lastname: Saini
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäuerle
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.forename: Tim
authors.initials: T
authors.lastname: Holland-Letz
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfner
authors.forename: Martin
authors.initials: M
authors.lastname: Sprick
authors.forename: Martina
authors.initials: M
authors.lastname: Scharpff
authors.forename: Frederik
authors.initials: F
authors.lastname: Marmé
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Sinn
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D002452:Cell Count; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor