Cancer stem cells in solid tumors: elusive or illusive?

Abstract

During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a) a stringent definition of cancer stem cells in solid tumors (b) specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare.In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

Figure 1

Origin of Cancer stem cells. In normal tissue, stem cells (green) divide asymmetrically into progenitor cells (orange) from which then terminally differentiated cells (red) are produced (left). In tumorigenesis mutations can transform stem cells into cancer stem cells (light blue) which then result in tumorigenic progenitor cells and differentiated tumor cells (dark blue). But also, by mutations in developmental pathways progenitor cells and differentiated cells can re-acquire stem cell-like properties and turn into cancer stem cells (right).

Figure 2

Relationship between stem cell species. Stem cells are characterized by their ability to form many different types of tissues and their capacity to self-renew. With increasing level of differentiation from progenitor cell to differentiated cell, the plasticity reduces as does the proliferative capacity. Cancer stem cells form at the interface between stem cell and progenitor cells. This phenomenon has lately also been credited to iPS cells and their partially reprogrammed precursors.