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Cancer stem cells: Common as muck

Nature Reviews Cancer 9, 6-7 (January 2009) | doi:10.1038/nrc2563
http://www.nature.com/nrc/journal/v9/n1/full/nrc2563.html
Safia Ali Danovi

It's not easy being a cancer stem cell.
They have been blamed for single-handedly propelling tumour growth, along with mediating other evils such as chemoresistance and radioresistance.
It is thus contended that the key to conquering cancer lies in their annihilation. However, others have argued that the existence of cancer stem cells in solid tumours relies on results derived from artificial experimental conditions that bear little resemblance to the in vivo situation in a tumour. Recent data from Sean Morrison and colleagues provide ammunition for the naysayers.

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.

Taken together, these data indicate that tumour-initiating cells are far more common than previous reports have suggested, and the authors further reinforced this idea by injecting single cells obtained from xenografted melanomas into mice and showing that as many as 27% of injections resulted in tumour formation. Moreover, extensive analysis of over 50 surface markers — including the 'cancer stem cell marker' CD133 — failed to discriminate between tumorigenic and non-tumorigenic cells, suggesting that cells that have poor tumorigenic capacity under certain conditions may in fact readily form tumours in others.

...tumorigenic cells are far more common than previous reports have suggested...
The authors grant that no data thus far provide insight into the question of whether a specific population of cells contributes to tumour progression in patients, and admit that a distinct population of cells capable of propelling tumour growth might yet be identified. They show, however, that the commonly used NOD/SCID assay significantly underestimates the frequency of human cells with tumorigenic potential. Thus, some cancers that have only few tumorigenic cells in NOD/SCID mice, such as melanomas, actually have many tumorigenic cells under other assay conditions. So, whereas the cancer stem cell model probably holds true for certain cancers, other paradigms might be in play for others.

References and links
ORIGINAL RESEARCH PAPER
Quintana, E. et al. Efficient tumour formation by single human melanoma cells. Nature 456, 593–598 (2008)