Cancer stem cells (CSCs), which comprise a small fraction of cancer cells, are believed to constitute the origin of most human tumors. Considerable effort has been focused on identifying CSCs in multiple tumor types and identifying genetic signatures that distinguish CSCs from normal tissue stem cells. Many studies also suggest that CSCs serve as the basis of metastases. Yet, experimental evidence that CSCs are the basis of disseminated metastases has lagged behind the conceptual construct of CSCs. Recent work, however, has demonstrated that CSCs may directly or indirectly contribute to the generation of metastasis. Moreover, CSC heterogeneity may be largely responsible for the considerable complexity and organ specificity of metastases. In this review, we discuss the role of CSCs in metastasis and their potential as therapeutic targets.
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