Cancer stem cell (CSC) biology is a rapidly developing field within cancer research. CSCs are postulated to be a unique cell population exclusively capable of infinite self renewal, multilineage differentiation and with ability to evade conventional cytotoxic cancer therapy. These traits distinguish CSCs from their more differentiated counterparts, which possess only limited or no potential for self renewal and tumor initiation. Therefore, CSCs would be the driving motor of malignant growth and therapy resistance. Accordingly, successful cancer treatment would need to eliminate this highly potent group of cells, since even small residual numbers would suffice to recapitulate the disease after therapy. Putative CSCs has been identified in a broad range of human malignancies and several cell surface markers have been associated with their stem cell phenotype. Despite all efforts, a pure CSC population has not been isolated and often in vitro clonogenic and in vivo tumorigenic potential is found in several cell populations with occasionally contradictory surface marker signatures. Here, we give a brief overview of recent advances in CSC theory, including the signaling pathways in CSCs that also appear crucial for stem cells homeostasis in normal tissues. We discuss evidence for the interaction of CSCs with the stromal tumor environment. Finally, we review the emerging potentially effective CSC-targeted treatment strategies and their future role in therapy. ' 2012 International Society for Advancement of Cytometry
Key termscancer stem cells; cancer stem cell markers; cancer stem cell niche; therapy resistance CANCER stem cell (CSC) theory hypothesizes that heterogeneity within tumors is not a mere consequence of random mutation and clonal evolution, but results from an intrinsic hierarchy of cells, with the putative CSC at the apex of the hierarchy (1,2). The CSC is thought to share several key features with normal stem cells: unlimited capacity for self renewal, including maintenance of the CSC population through asymmetric division, the ability to differentiate into several cell lineages and intrinsic resistance against cytotoxic therapies through drug-efflux mechanisms and slow cell cycling (2). CSC theory postulates that not all tumor cells are equal with regard to self-renewal, tumor initiation, and maintenance potential, these traits being reserved for the CSC population. Additionally, cellular heterogeneity and hierarchy within the tumor originates from CSCs, which give rise to daughter cells that proliferate and differentiate into the cell mass that compromises a significant portion of the bulk tumor (1). Further, CSCs are thought to be responsible for therapy resistance, minimal residual disease and relapse after initial successful therapy, their stem-like features making them able to evade conventional treatment modalities (3). It has also been implied that these stem cell traits allow CSCs to play a leading role in metastasis (4-6).Since the first experiments verifying that a specific phenotype wi...