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Anstine et al. J Cancer Metastasis Treat 2019;5:50 Journal of Cancer
DOI: 10.20517/2394-4722.2019.24 Metastasis and Treatment

Review Open Access

A new view of the mammary epithelial hierarchy
and its implications for breast cancer initiation and

metastasis

Lindsey J. Anstine , Ruth Keri 1,2
1
1 Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
2 Department of Genetics and Genome Sciences and Department of General Medical Sciences-Oncology, Case Western Reserve
University, Cleveland, OH 44106, USA.
Correspondence to: Dr. Ruth Keri, Pharmacology, CWRU School of Medicine, Case Western Reserve University, 2109 Adelbert
Road, Cleveland, OH 44106, USA. E-mail: ruth.keri@case.edu

How to cite this article: Anstine LJ, Keri R. A new view of the mammary epithelial hierarchy and its implications for breast cancer
initiation and metastasis. J Cancer Metastasis Treat 2019;5:50. http://dx.doi.org/10.20517/2394-4722.2019.24

Received: 12 Mar 2019 First Decision: 10 Apr 2019 Revised: 27 Apr 2019 Accepted: 7 May 2019 Published: 13 Jun 2019

Science Editor: William Schiemann Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract

The existence of mammary epithelial stem cell (MaSC) populations capable of mediating mammary gland
development and homeostasis has been established for over a decade. A combination of lineage tracing and
mammary gland transplantation studies has affirmed that MaSCs and their downstream progenitors are organized
in a hierarchal manner; however, these techniques have failed to illuminate the complete spectrum of epithelial
intermediate populations or their spatial and temporal relationships. The advent of single cell sequencing
technology has allowed for characterization of highly heterogeneous tissues at high resolution. In the last two
years, the remarkable advances in single cell RNA sequencing technologies have been leveraged to address the
heterogeneity of the mammary epithelium. These studies have afforded fresh insights into the transcriptional
differentiation hierarchy and its chronology. Importantly, these data have led to a major conceptual shift in which
the rigid boundaries separating stem, progenitor, and differentiated epithelial populations have been deconstructed,
resulting in a new more fluid and flexible model of epithelial differentiation. The emerging view of the mammary
epithelial hierarchy has important implications for mammary development, carcinogenesis, and metastasis,
providing novel insights into the underlying cellular states that may promote malignant phenotypes.

Keywords: Mammary gland, mammary epithelial cells, breast cancer, stem cell

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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