CD10: A tool to crack the role of stem cells in breast cancer

Keller et al. (1) highlighted the use of the CD10 and epithelial cell adhesion molecule (EpCAM) markers to discriminate basal from luminal breast epithelial subpopulations. Based on the same two markers, we have previously developed a simple, robust, and reliable flow cytometry sorting technique to separate luminal populations cleanly from the rest of precursor cells (2). The various functional assays we used have established that EpCAM+ separates luminal progenitors from other epithelial populations present in the CD10+ fraction (stem cells, early and bipotent progenitors, and later myoepithelial lineage cells). In addition, we have identified CD10-enzyme as an easy-to-use cell surface tool to isolate sphere-forming cells from a variety of other normal human adult tissues. Despite the similar results on the characterization of the two epithelial subpopulations, there is an apparent discrepancy between our findings, which suggest that this sphere-forming ability is linked to CD10+ cells (2), and the paper of Keller et al. (1), which related this property to EpCAM+ cells. This difference is likely attributable to the sorting strategy, the culture media, and the criteria used for mammosphere scoring. As noted by Keller et al. (figure S2C and corresponding legend of ref. 1), they defined mammosphere based on physical criteria that are influenced by the processing protocol applied. In our case, we have considered as mammospheres a group of cells (over 100) growing as floating, dense, and compact aggregates and surrounded by a membrane-like structure that makes them look very much like embryonic bodies. Regardless of these differences, both our results and those of Keller et al. (1) suggest a potential value of CD10 expression in mammary stem cells. We have also demonstrated the key role of CD10 not only as a cell surface marker but as a full functional regulator of normal mammary progenitor cells. Indeed, our work also indicates that a gradient of biological peptides generated by CD10-enzyme cleavage is involved, with β1-integrins, in maintaining stem cells/early progenitors and regulating their conversion to luminal progenitors. This illustrates the dual role of CD10 in this system as already pointed out by Kenny et al. (3) years ago. In addition, different data in the literature suggest that CD10 and its enzymatic functions might act as a stem cell regulator in a number of cellular compartments (reviewed in 4).