Abstract
Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.
Highlights
The mammary gland epithelium is hierarchically organized and composed of two main cellular lineages: the basal/myoepithelial cells with contractile capacity, and the luminal cells with milk productive function [1,2]
The identification and comprehension of mammary stem cells (MaSCs) biology has tremendously impacted our knowledge of breast cancer stem cells (CSCs)
New technologies have allowed for the identification of adult MaSCs, the existence of breast cancer stem cells (bCSCs), and proven cellular plasticity
Summary
The mammary gland epithelium is hierarchically organized and composed of two main cellular lineages: the basal/myoepithelial cells with contractile capacity, and the luminal cells with milk productive function [1,2]. Within this structure, the multipotent mammary stem cells (MaSCs) are at the top of the hierarchy, giving rise to progenitor cells and differentiated cells of both lineages [1,3,4]. Sca-1− [7,8] These populations displayed myoepithelial features and multipotency to regenerate the entire functional gland after transplantation, in such perturbed regenerative conditions, adult MaSCs are bipotent and have myoepithelial properties [9]. A better understanding of mammary stem cell biology is essential to better understand the differences and weaknesses of bCSCs and unveil specific molecular targets with therapeutic applications to halt breast cancer progression
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