Implications of Cancer Stem Cells for Tumor Metastasis

Metastasis is the dissemination of cancer cells from primary tumors to distant sites. This phenomenon accounts for greater than 90% of deaths associated with cancer (1). Dissemination of cancer cells is a complex process involving a sequence of diverse functional steps, such as detachment from the primary tumor tissue, migration and homing to a different anatomical site, and survival and growth into a metastatic cancerous lesion. Traditional observations suggest that this phenomenon is mediated by late-stage genetic alterations which program cancer cells for active mobilization and distant-site engraftment. With the discovery that solid tumors may be driven in their growth by subsets of cancer cells selectively endowed with tumor-initiating capacity—also termed cancer stem cells (CSCs)—tumor progression has come under new investigation. These cells exhibit properties reminiscent of normal tissue stem cells: they are a phenotypically unique subset of cells capable of recapitulating the morphologic and phenotypic diversity of the original tumor when serially transplanted in immunodeficient mice. Given their preferential capacity to self-renew and form new tumor lesions, these cells have been postulated to play a key role in metastatic cancer. Moreover, gene expression studies have recently demonstrated a high correlation between CSC gene expression profiles, the risk of metastasis, and patient survival. In this chapter, we aim to discuss the implications of the CSC theory in metastatic cancer. We will begin by introducing CSCs, drawing functional parallels between them and normal stem cells. We will then discuss their biology and highlight their clinical relevance. Further study of CSCs is important as they may hold potential for specific therapeutics aimed at reducing or eliminating the tumor load by eradicating the source of the tumor, the cells that initiate and sustain cancerous growth.