The problem with all of the so-called stem cells markers is that even combinations of them select a subpopulation only a tiny subfraction of which are the stem cells. One may enrich for stem cells using these markers, but even so, only a tiny fraction of the enriched population will be the stem cells. We have shown that for breast cancer stem cells (CSCs), of the triple-marker selected population (CD24-CD44+CD326+ = 2% of tumor) only 1% are functionally CSCs; i.e., 1% of 2% = 0.02% were CSCs. This is consistent with the 0.04% we got without any enrichment, using our Hybrid Spheroid Assay. See: In measuring the radiosensitivity of breast cancer stem cells (CSCs), cell surface biomarkers purporting to designate a CSC “phenotype” are an insufficient definition of CSCs, since > 98% are not CSCs. Christopher S. Lange, Talal Syed, Paul K. Valestra, Erica Lai, Anna Groysman, Shy’Ann Jie, Manuj Agarwal, Elliot Navo, Robert Rotman, Lisa Dresner, Bozidar Djordjevic. Radiat. Res. 58th Annual Meeting Program Book: pg 126-127, Abstract PS5-48, September 30 – October 3, 2012, San Juan, PR.
Stem cells (and CSCs) tend to be only a fraction of a % of the total tissue of interest, so any cell-surface marker selection process that yields stem cell fractions in the order of 1 - 10%, or higher, includes many non-stem cells.
Dr Lange's point is very true, which is why we developed a better method of detecting CSC based on the TRUE stem cell markers Nanog and Sox-2. If the cell doesn't express these markers it is not a cancer stem cell!
mRNA detection in living cells: A next generation cancer stem cell identification technique.
McClellan S, Slamecka J, Howze P, Thompson L, Finan M, Rocconi R, Owen L.
Nanog is fine for epithelial CSCs, but not for mesenchymal. We used Oct4 and vimentin for mesenchymal and Oct4 plus Nanog for epithelial CSCs. However, the staining was on fixed cells. Our HSA allows us to measure the number and sensitivity to treatments of individual patient CSCs, based on their functional behavior (per Till & McCulloch).