emss-75771.pdf (3.75 MB)
Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours
journal contributionposted on 2020-07-01, 17:09 authored by Leander Blaas, Fabio Pucci, Hendrik A Messal, Agneta B Andersson, E Josue Ruiz, Marco Gerling, Iyadh Douagi, Bradley Spencer-Dene, Alexandra Musch, Richard Mitter, Leena Bhaw, Richard Stone, Dorothee Bornhorst, Abdul K Sesay, Jos Jonkers, Gordon Stamp, Ilaria Malanchi, Rune Toftgård, Axel Behrens
The mammary gland is composed of a complex cellular hierarchy with unusual postnatal plasticity. The identities of stem/progenitor cell populations, as well as tumour-initiating cells that give rise to breast cancer, are incompletely understood. Here we show that Lgr6 marks rare populations of cells in both basal and luminal mammary gland compartments in mice. Lineage tracing analysis showed that Lgr6+ cells are unipotent progenitors, which expand clonally during puberty but diminish in adulthood. In pregnancy or following stimulation with ovarian hormones, adult Lgr6+ cells regained proliferative potency and their progeny formed alveoli over repeated pregnancies. Oncogenic mutations in Lgr6+ cells resulted in expansion of luminal cells, culminating in mammary gland tumours. Conversely, depletion of Lgr6+ cells in the MMTV-PyMT model of mammary tumorigenesis significantly impaired tumour growth. Thus, Lgr6 marks mammary gland progenitor cells that can initiate tumours, and cells of luminal breast tumours required for efficient tumour maintenance.
AllelesAnimalsAnimals, NewbornBreast NeoplasmsCarcinogenesisCell LineageCell ProliferationClone CellsDisease-Free SurvivalDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHomeostasisHormonesHumansMammary Glands, AnimalMammary Neoplasms, ExperimentalMiceNeoplastic Stem CellsPregnancyReceptors, G-Protein-CoupledStem CellsUp-RegulationBehrens FC001039Malanchi FC001112HPCBASDevelopmental Biology06 Biological Sciences11 Medical and Health Sciences