Receptor Activator of NF-κB Ligand Promotes Proliferation of a Putative Mammary Stem Cell Unique to the Lactating Epithelium§

Authors

  • Elizabeth Thomas,

    Corresponding author
    1. School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Perth, Western Australia, Australia
    2. School of Surgery, The University of Western Australia, Perth, Western Australia, Australia
    3. St John of God Hospital, Subiaco, Western Australia, Australia
    • Bendat Comprehensive Cancer Centre (Level 5), St John of God Hospital, 12 Salvado Road, Subiaco, Western Australia 6008, Australia
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    • Telephone: 61-8-9213-2108; Fax: 61-8-9381-7915;

  • Tracey Lee-Pullen,

    1. Centre for Microscopy, Characterization and Analysis, The University of Western Australia, Perth, Western Australia, Australia
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  • Paul Rigby,

    1. Centre for Microscopy, Characterization and Analysis, The University of Western Australia, Perth, Western Australia, Australia
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  • Peter Hartmann,

    1. School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Perth, Western Australia, Australia
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  • Jiake Xu,

    1. School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia
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  • Nikolajs Zeps

    1. School of Surgery, The University of Western Australia, Perth, Western Australia, Australia
    2. St John of God Hospital, Subiaco, Western Australia, Australia
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  • Author contributions: E.T.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; T.L.-P.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; P.R.: data analysis and interpretation and final approval of manuscript; P.H.: provision of study material and patients, financial support, and final approval of manuscript; J.X.: conception and design, provision of study material, data analysis and interpretation, and final approval of manuscript; N.Z.: manuscript writing and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS March 30, 2012.

Abstract

In mice, CD49fhi mammary stem cells (MaSCs) asymmetrically divide to generate CD49f+ committed progenitor cells that differentiate into CD49f phenotypes of the milk-secreting tissue at the onset of pregnancy. We show CD49f+ primary mammary epithelial cells (PMECs) isolated from lactating tissue uniquely respond to pregnancy-associated hormones (PAH) compared with CD49f+ cells from nonlactating tissue. Differentiation of CD49f+ PMEC in extracellular matrix produces CD49f luminal cells to form differentiated alveoli. The PAH prolactin and placental lactogen specifically stimulate division of CD49f luminal cells, while receptor activator of nuclear factor (NF)-κB ligand (RANKL) specifically stimulates division of basal CD49f+ cells. In nondifferentiating conditions, we observed a greater proportion of multipotent self-renewing cells, and RANKL treatment activated the RANK pathway in these cultures. Furthermore, we observed the deposition of calcium nodules in a proportion of these cells. These data imply that a MaSC unique to the lactating breast exists in humans, which generates progeny with discrete lineages and distinct response to PAH. STEM CELLS2012;30:1255–1264

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