Mammary Stem Cells: Premise, Properties, and Perspectives

Abstract

Adult mammary stem cells (MaSCs) drive postnatal organogenesis and remodeling in the mammary gland, and their longevity and potential have important implications for breast cancer. However, despite intense investigation the identity, location, and differentiation potential of MaSCs remain subject to deliberation. The application of genetic lineage-tracing models, combined with quantitative 3D imaging and biophysical methods, has provided new insights into the mammary epithelial hierarchy that challenge classical definitions of MaSC potency and behaviors. We review here recent advances - discussing fundamental unresolved properties of MaSC potency, dynamics, and plasticity - and point to evolving technologies that promise to shed new light on this intractable debate. Elucidation of the physiological mammary differentiation hierarchy is paramount to understanding the complex heterogeneous breast cancer landscape.

WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis

“…Our study utilized a system with penetrant and specific labeling of cap cells in the TEB to confirm that cap cells are unipotent, supporting the findings of Scheele et al (Scheele et al, 2017). However, given that our lineage-tracing model is not specific for cap cells, but rather labels the entire basal epithelium, a cap cell-specific fate mapping approach exploiting markers such as s-ship , as has been recently suggested (Lloyd-Lewis et al, 2017), is required to definitively confirm our observations of cap cell unipotency.…”

Mammary mechanobiology: mechanically-activated ion channels in lactation and involution

“…Similar signal duplication with chemical domination may also exist in mammalian cells and systems. Indeed, remarkable redundancy in the creation of the alveolar epithelium by mammary stem/progenitor cells has already been observed in this evolutionarily essential organ (3,7).…”

“…The adult mammary epithelium consists of an arborized ductal network embedded within an adipose stroma (1). The ductal epithelium contains both luminal and basal cells, which are produced and maintained postnatally by lineage-restricted precursors (2)(3)(4)(5)(6)(7). During gestation, a coordinated program of epithelial proliferation, side-branching, differentiation and tissue remodeling takes place (1,8), resulting in the generation of thousands of alveolar structures that adorn the central ductal epithelium in lobular clusters (9).…”

Breast Cancer: Multiple Subtypes within a Tumor?

“…In fact, there are reports of more differentiated luminal breast cancer cells exhibiting equal tumor initiating capacity as basal/stem-like breast cancer cells [13, 19]. Further insights and elucidation of the normal mammary hierarchy, which are extensively covered by these reviews [20, 21, 32], will be vital to the understanding of various distinct CSC populations in breast tumors. Additionally, comprehension of the intrinsic and niche factors that govern each of the normal mammary stem/progenitor cell states may shed light on the vulnerabilities of distinct CSC populations.…”