title: Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids.
abstract: The development of in vitro culture systems quantitatively and qualitatively recapitulating normal breast biology is key to the understanding of mammary gland biology. Current three-dimensional mammary culture systems have not demonstrated concurrent proliferation and functional differentiation ex vivo in any system for longer than 2 weeks. Here, we identify conditions including Neuregulin1 and R-spondin 1, allowing maintenance and expansion of mammary organoids for 2.5 months in culture. The organoids comprise distinct basal and luminal compartments complete with functional steroid receptors and stem/progenitor cells able to reconstitute a complete mammary gland in vivo. Alternative conditions are also described that promote enrichment of basal cells organized into multiple layers surrounding a keratinous core, reminiscent of structures observed in MMTV-Wnt1 tumours. These conditions comprise a unique tool that should further understanding of normal mammary gland development, the molecular mechanism of hormone action and signalling events whose deregulation leads to breast tumourigenesis.
authors: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.|Cancer Program, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria 3800, Australia.|Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.|Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
authors: Thierry
authors: T
authors: Jardé
authors: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.|Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors: Bethan
authors: B
authors: Lloyd-Lewis
authors: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors: Mairian
authors: M
authors: Thomas
authors: European Cancer Stem Cell Research Institute, Cardiff School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UK.
authors: Howard
authors: H
authors: Kendrick
authors: Division of Breast Cancer Research, Breast Cancer Now, Institute of Cancer Research, London SW3 6JB, UK.
authors: Lorenzo
authors: L
authors: Melchor
authors: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors: Lauriane
authors: L
authors: Bougaret
authors: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors: Peter D
authors: PD
authors: Watson
authors: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors: Kenneth
authors: K
authors: Ewan
authors: European Cancer Stem Cell Research Institute, Cardiff School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UK.
authors: Matthew J
authors: MJ
authors: Smalley
authors: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors: Trevor C
authors: 0000-0002-4880-9963
authors: TC
authors: Dale
mesh_terms: D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007621:Karyotyping; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D009940:Organoids / Q000254:growth & development / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*; D066247:Receptor, ErbB-4 / Q000235:genetics / Q000378:metabolism*; D059008:Time-Lapse Imaging / Q000379:methods; D046509:Tissue Culture Techniques / Q000379:methods; D060449:Wnt Signaling Pathway
chemical_list: D020890:Neuregulin-1; C000607800:ErbB3 protein, mouse; C587690:Erbb4 protein, mouse; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4