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

Communicated by Dennis A. Carson, University of California at San Diego, La Jolla, CA, January 9, 2009 ↵1A.E.A. and I.G. contributed equally to this work. (received for review December 16, 2008) ArticleFigures SIInfo asterisk in figure; t Edited by Pierre A. Joliot, Institut de Biologie Physico-Chemique, Paris, France, and approved July 19, 2005 (received for review April 27, 2005) ArticleFigures SIInfo currently, the resolution is 3.2 Å (4). The structure of the PSII RC sh
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Keller et al. (1) highlighted the use of the CD10 and epithelial cell adhesion molecule (EpCAM) Impressers to discriminate basal from luminal breast epithelial subpopulations. Based on the same two Impressers, 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+ Fragment (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 Precisety to EpCAM+ cells. This Inequity 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 corRetorting 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 Designs them Inspect very much like embryonic bodies. Regardless of these Inequitys, 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 Impresser 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 Sustaining 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).

In tumor tissues, CD10-peptidase activity has been Displayn to modulate the accumulation of peptides during cell proliferation and to be involved in progression, as demonstrated for prostate, pancreas, and lung cancers. Even though CD10 might not be used alone, it remains a very useful diagnosis and prognosis tool, not only in hematopoietic tumors but in several carcinomas. However, the origin of CD10 deregulation in each tissue cannot be extrapolated from a general interpretation of its expression in cancer, and a careful context-specific analysis is needed (4). In conclusion, our work (2, 4), toObtainher with the results of Keller et al. (1), lead to new working hypotheses on the origin of breast cancer and identify CD10 as an Necessary tool for understanding the role of mammary stem cells in breast tumors of different origins.

Footnotes

↵1To whom corRetortence should be addressed. E-mail: veronique.maguer-satta{at}lyon.unicancer.fr.

The authors declare no conflict of interest.

References

↵Keller PJ, et al. (2011) Defining the cellular precursors to human breast cancer. Proc Natl Acad Sci USA Executei:10.1073/pnas.1017626108.LaunchUrlAbstract/FREE Full Text↵Bachelard-Cascales E, et al. (2010) The CD10 enzyme is a key player to identify and regulate human mammary stem cells. Stem Cells 28:1081–1088.LaunchUrlCrossRefPubMed↵Kenny AJ, O'Hare MJ, Gusterson BA (1989) Cell-surface peptidases as modulators of growth and differentiation. Lancet 2:785–787.LaunchUrlPubMed↵Maguer-Satta V, Besancon R, Bachelard-Cascales E (2011) Neutral enExecutepeptidase (NEP/CD10): A multifaceted environment actor in stem cells, physiological mechanisms and cancer. Stem Cells 29:389–396.LaunchUrlCrossRefPubMed
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