En Route to Metastasis: Circulating Tumor Cell Clusters and Epithelial-to-Mesenchymal Transition

Blood-borne metastasis accounts for the vast majority of cancer-related deaths and it is fueled by the generation of circulating tumor cells (CTCs) from a primary tumor deposit. Recent technological advances have made it possible to characterize human CTCs as they travel within the bloodstream. CTCs are found both as single cells and as clusters of cells held together by intercellular junctions. Although less prevalent, CTC clusters appear to have greater metastatic potential than single CTCs in the circulation. Both may exhibit shifts in expression of epithelial and mesenchymal markers, which may show dynamic changes during cancer progression. In this review we discuss recent insights into the biological properties of individual and clustered cancer cells in the circulation.