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.
Highlights
Already 150 years ago, the German pathologist Rudolf Virchow postulated in his theory of the cellular pathology that cancer initiates from immature cells [1]
If cancer stem cells (CSC) are really enriched in this population, these cells should have a several fold higher capacity to form tumors compared to the control fraction where the cells lack this CSC marker or the typical characteristics as rapid efflux of Hoechst due to high expression of ATP-Binding Cassette (ABC) transporters
The concept of cancer stem cells was very welcome because it opened new perspectives in understanding and healing this disease
Summary
Already 150 years ago, the German pathologist Rudolf Virchow postulated in his theory of the cellular pathology that cancer initiates from immature cells [1]. If CSCs are really enriched in this population, these cells should have a several fold higher capacity to form tumors compared to the control fraction where the cells lack this CSC marker or the typical characteristics as rapid efflux of Hoechst due to high expression of ABC transporters In this manner, the side population after Hoechst staining and flow cytometric analysis was proved to be enriched of tumor-initiating cells in thyroid [54], ovarian [78] and breast cancer [46], glioma [46,53], melanoma [70] and hepatocellular carcinoma [79]. Keeping this in mind one has to be very careful when interpreting the current literature on cancer stem cells
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