Cancer stem cell surface markers do not correlate with tumorigenicity in vivo

by Alexey Bersenev on January 29, 2013 · 0 comments

in cancer

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We’ve written about phenotypic plasticity of cancer stem cells (CSC) and validity of their surface markers.

Recently, more studies were published, which support the notion that common CSC surface markers are useless. In the Chinese study, published in PLoS ONE, multiple common CSC markers from primary tumors and cell lines (leukemias, breast cancer, glioblastoma) were tested in number of assays. The authors concluded:

… tumorigenic cells cannot be distinguished by common CSC markers alone and we propose that cautions should be taken when using these markers independently to identify cancer stem cells due to the phenotypic plasticity of tumor cells.

The key assay was a tracing of labeled CSC mixed with non-CSC in xenotransplantation model. This is very interesting approach, which clinically more relevant. Seem like the use conventional xenotransplantation assays (purified CSC+ versus CSC- populations) can underestimate the tumorigenicity of CSC- populations:

It was found that CSC− cells exhibited similar proliferative and tumorigenic capacities as CSC+ cells when the two subsets coexisted.

So mixing and tracing it makes a lot of sense. Interestingly, both transplanted CSC+ and CSC- gave both CSC+ and CSC- progeny. It indicates to the markers reversibility and absence of hierarchy.

Another recent study unveiled the problems with not only surface, but with genetic and functional breast cancer markers as well:

In vitro cell cycle kinetics and in vivo tumor doubling times displayed no difference between sphere and monolayer cultures. Our data indicate that intrinsic genetic and functional markers investigated are not indicative of the in vivo tumorigenicity of putative breast tumor-initiating cells.

Finally, the validity of the most “popular” CSC in neuro-oncology CD133 was critisized in the recent review:

… the suggestion that CD133 may be a central ‘holy grail’ in identifying core cells for propagation of malignant glial neoplasms seems increasingly less convincing.

The validity of markers in oncology is a big problem. The use of valid markers for CSC detection is ongoing debate. It could change our view on cancer development and clinical strategies in oncology.

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