Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours
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
10779/crick.12595148.v1
https://crick.figshare.com/articles/journal_contribution/Lgr6_labels_a_rare_population_of_mammary_gland_progenitor_cells_that_are_able_to_originate_luminal_mammary_tumours/12595148
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.
2020-07-01 17:09:49
Alleles
Animals
Animals, Newborn
Breast Neoplasms
Carcinogenesis
Cell Lineage
Cell Proliferation
Clone Cells
Disease-Free Survival
Drug Resistance, Neoplasm
Female
Gene Expression Regulation, Neoplastic
Homeostasis
Hormones
Humans
Mammary Glands, Animal
Mammary Neoplasms, Experimental
Mice
Neoplastic Stem Cells
Pregnancy
Receptors, G-Protein-Coupled
Stem Cells
Up-Regulation
Behrens FC001039
Malanchi FC001112
HP
CB
AS
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences