期刊
NATURE BIOTECHNOLOGY
卷 31, 期 6, 页码 539-U143出版社
NATURE PORTFOLIO
DOI: 10.1038/nbt.2576
关键词
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资金
- BioRN Spitzencluster Molecular and Cell Based Medicine
- German Bundesministerium fur Bildung und Forschung
- EU FP7 Program EuroSyStem
- Sonderforschungsbereich [SFB-873]
- Deutsche Forschungsgemeinschaft
- TIME consortium Project
- Dietmar Hopp Foundation
- European Research Council Advanced Investigator Grant DISSECT [269081]
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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