Fundamental Relationships Between Cancer Stem Cells, the Cancer Stem Cell Niche and Metastasis

Parallels drawn between stem cells and cancer are not new. However, these shared features are becoming increasingly important as our understanding of disseminated, recurrent and metastatic cancer cell biology continues to develop. Indeed, nearly all cancer-related deaths are the result of recurrent and metastatic disease, highlighting the need for a more comprehensive schema of how tumors colonize new sites, resist therapy and evolve. In this chapter, we compare the phenotypes of stem cells, cancer stem cells (CSCs) and metastatic cells, highlighting notable points of contrast. We begin with an introduction to stem cell biology, tumorinitiating CSCs, metastatic cells and discuss shared features. The implication of the stem-like phenotype extends to many characteristics of cell biology: cell division, differentiation, morphology, gene expression, motility, invasion, clonogenicity, capacity for colonization, metabolism and the interaction of these cells with their surrounding microenvironment. Stem cell phenotypes are highly complex and, while there may be a number of shared features, there are important elements that are uniquely tissue-dependent. While staunch definitions based upon a single biomarker of stemness have proven inadequate in broader applications, seeing universal themes of the stem cell phenotype will provide critical insights for studying cancer. Our understanding of this complex biology is critical for developing rational and dynamic therapeutic interventions for patients with recurrent and metastatic cancer.

Keywords: Biomarker, Cancer stem cell, Cancer stem cell niche, Clonogenicity, Dissemination, Dormancy, Epithelial-mesenchymal transition, Heterogeneity, Metabolism, Metastasis, Metastasis-initiating cells, Metastatic cell, Metastatic colonization, Metastatic niche, Pluripotency, Quiescence, Review, Self-renewal, Stem cell, Stem cell niche, Tumor progression, Tumorigenesis, Tumorigenic cells, Tumor-initiating cell.