title: Receptor activator of NF-κB ligand promotes proliferation of a putative mammary stem cell unique to the lactating epithelium.
abstract: In mice, CD49f(hi) 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.
authors.affiliation: School of Biomedical, Biomolecular and Chemical Sciences, Subiaco, Western Australia, Australia. libbythomas@westnet.com.au
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thomas
authors.forename: Tracey
authors.initials: T
authors.lastname: Lee-Pullen
authors.forename: Paul
authors.initials: P
authors.lastname: Rigby
authors.forename: Peter
authors.initials: P
authors.lastname: Hartmann
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
authors.forename: Nikolajs
authors.initials: N
authors.lastname: Zeps
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D039503:Integrin alpha6 / Q000096:biosynthesis; D007774:Lactation; D042361:Mammary Glands, Human / Q000166:cytology* / Q000378:metabolism; D008895:Milk, Human / Q000166:cytology; D011247:Pregnancy; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*
chemical_list: D039503:Integrin alpha6; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505688:TNFSF11 protein, human