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

New bioengineering technologies allow detailed characterization of circulating tumor cells (CTCs). These rare populations of cancer cells in transit within the blood circulation hold the key to understanding the process of human cancer metastasis. While most CTCs are single cells, a small fraction travel as groups of cells. In mouse models, CTC clusters derive from individual tumor fragments and exhibit far greater metastatic potential than single CTCs. Dynamic changes in epithelial and mesenchymal markers are evident within CTCs as patients initially respond and ultimately progress on cancer therapies, pointing to considerable plasticity of cell fates in cancer cells that evolve in response to treatment. 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. 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. Metastasis: Circulating Tumor Cells in Small Cell Lung CancerHamilton et al.Trends in CancerMarch 19, 2016In BriefSmall cell lung cancer (SCLC) is distinguished by excessive numbers of circulating tumor cells (CTCs) in extended and recurring disease. This malignancy has a poor prognosis due to rapid emergence of chemoradioresistant relapses after first-line chemotherapy. In vitro expansion of several CTC lines allowed for a detailed study of the contribution of these cells to metastasis. Generation of CTCs involves the establishment of co-cultures and recruitment of macrophages and specific cytokines. All cell lines show E-cadherin-positive epithelial-like cells and spontaneous assembling into very large tumorospheres. Full-Text PDF