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M. H. Cruz 1 and Å. Sidén 1,2 and G. M. Calaf 3,4 and Z. M. Delwar 1 and J. S. Yakisich 1
Recommended by H. Rizos and G. Schiavon
1, Department of Clinical Neuroscience R54, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
2, Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
3, Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile
4, Center for Radiological Research, Columbia University Medical Center, New York, NY, USA
Received 26 April 2012; Accepted 23 May 2012
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
The identification of putative cancer stem cells (CSCs) in tumors some years ago gave rise to new concepts in cancer biology, and consequently new dogmas in the cancer field were established. The classical cancer stem cells model (CSM) proposes that all cancer types have a subpopulation of cancer stem cell responsible for resistance to chemo- and/or radiotherapy, concluding that eliminating this subpopulation of CSCs will cure cancer [1-5]. However, there is no consensus among experimental data regarding key issues that are important for the establishment of effective treatments. For instance, the percentage of cancer stem cells detected in glioma cell lines tumors varies from less than 1% to 100% (for review see [6]). The differences have also been observed in other types of cancer (see below). However, these discrepancies, which might be well due to differences in methodology and criteria used to detect and characterize these cells have important clinical consequences. If the percentage of CSCs is rare (<1%), the elimination (if feasible) of this fraction with some kind of targeted treatment would indeed be a success, providing that non-cancer stem cells (non-CSCs) are easily controlled by other cytotoxic or cytostatic therapies. In the other extreme scenario, where 100% of cancer cells are CSCs, the effective therapy will require a novel treatment able to eliminate 100% of cancer cells at once in order to prevent regrowth.
Based on our observations of proliferation kinetics of mixed cell cultures, we have developed a novel model of glioma biology (Stemness Phenotype Model, SPM), which proposes that all glioma cells have the potential...