Identification of a Population of Blood Circulating Tumor Cells from Breast Cancer Patients That Initiates Metastasis in a Xenograft Assay

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2013 Apr 24

PMID 23609047

Citations 545

Authors

Irene Baccelli

Andreas Schneeweiss

Sabine Riethdorf

Albrecht Stenzinger

Anja Schillert

Vanessa Vogel

Corinna Klein

Massimo Saini

Tobias Bauerle

Markus Wallwiener

Tim Holland-Letz

Thomas Hofner

Martin Sprick

Martina Scharpff

Frederik Marme

Hans Peter Sinn

Klaus Pantel

Wilko Weichert

Andreas Trumpp

Affiliations

Soon will be listed here.

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.

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