The CD10 Enzyme Is a Key Player to Identify and Regulate Human Mammary Stem Cells

Abstract

The major components of the mammary ductal tree are an inner layer of luminal cells, an outer layer of myoepithelial cells, and a basement membrane that separates the ducts from the underlying stroma. Cells in the outer layer express CD10, a zinc-dependent metalloprotease that regulates the growth of the ductal tree during mammary gland development. To define the steps in the human mammary lineage at which CD10 acts, we have developed an in vitro assay for human mammary lineage progression. We show that sorting for CD10 and EpCAM cleanly separates progenitors from differentiated luminal cells and that the CD10-high EpCAMlow population is enriched for early common progenitor and mammosphere-forming cells. We also show that sorting for CD10 enriches sphere-forming cells from other tissue types, suggesting that it may provide a simple tool to identify stem or progenitor populations in tissues for which lineage studies are not currently possible. We demonstrate that the protease activity of CD10 and the adhesion function of b1-integrin are required to prevent differentiation of mammary progenitors. Taken together, our data suggest that integrin-mediated contact with the basement membrane and cleavage of signaling factors by CD10 are key elements in the niche that maintains the progenitor and stem cell pools in the mammary lineage.

RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

“…S3A). Both phenotypes related with basal/ stem-like cells (16,17,20,21). RANKL stimulation for 48 hours further enhanced the changes induced by RANK, including the increased frequency of CD44 þ CD24 À (10% more) and CD10 cells, and the decreased EpCAM and CD49fhi ( Supplementary Fig.…”

“…We therefore looked at markers that have been related to stem cells and cancer stem cells in the human breast such as CD44, CD24, EpCAM, CD10, CD49f, and CD133 (15)(16)(17)(18)(19)(20) 2B and Supplementary Fig. S3A).…”

Quand les mutants de p53 se livrent à des trafics !

“…Le trafic intracellulaire des intégrines via les endosomes contrôle de nombreux processus liés à l'adhésion, tels que la motilité cellulaire, la cytokinèse et les interactions entre les intégrines et les récepteurs des facteurs de croissance [11]. De façon intéressante, les interactions des intégrines 1 avec leurs ligands (MEC) ont été impliquées dans le maintien des cellules souches dans leur niche et dans la régulation de leur quiescence [15,16]. Dans ce contexte, la stabilisation de l'expression des intégrines par l'interaction TAp63/p53 mutant pourrait contribuer au maintien et à la survie des cellules souches tumorales impliquées dans les rechutes et les résistances.…”

An analysis of stromal expression of CD10 in invasive ductal carcinoma of breast and its correlation with histological grade

“…22 In breast cancer loss of CD10 in myoepithelial cells leads to proliferation of malignant cells and invasion of in situ cancer. However, in invasive cancer expression of CD10 in stroma which characterize epithelial to mesenchymal transition (EMT), secreted from mesenchymal cells or transformed epithelial cancer stem cells, might prevent differentiation of cancer cells.…”