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.

Radial glial cells function during CNS development as neural progenitors, although their precise contribution to neurogenesis remains controversial. Recent work has argued that regional differences may exist regarding the neurogenic potential of radial glia. Here, we show that the vast majority of neurons in all brain regions derive from radial glia. Cre/loxP fate mapping and clonal analysis demonstrate that radial glia throughout the CNS serve as neuronal progenitors and that radial glia within different regions of the CNS pass through their neurogenic stage of development at distinct time points. Thus, radial glial populations within different CNS regions are not heterogeneous with regard to their potential to generate neurons versus glia.