A fundamental pillar of the cancer stem cell hypothesis is hierarchy, with cancer stem cells at the top of the pecking order — the biological equivalent of a hen's tooth. This dogma is based on the observation that only a minority of cells from a tumour have tumorigenic potential when xenotransplanted into non-obese diabetic, severe combined immunodeficient (NOD/SCID) mice. Based on this method, the frequency of melanoma-initiating cells has been estimated to be about 0.0001%. However, by modifying three xenotransplantation conditions — the strain of mouse used, the length of time over which the animals were followed, and mixing the cells with Matrigel prior to injection — Morrison's team could increase this frequency by several orders of magnitude. Importantly, the authors confirmed that these new experimental conditions were simply providing an environment that was more conducive for melanoma tumour formation, rather than inducing heritable changes in the cells themselves that could also have explained the observed increase in tumorigenicity. Furthermore, both xenografted human melanoma cells and freshly disassociated melanoma cells obtained directly from patients with either primary cutaneous or metastatic melanoma exhibited improved tumorigenicity under these new conditions, indicating again that the ability of cells to form tumours was more a function of environment than of cell type.
...tumorigenic cells are far more common than previous reports have suggested...
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