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Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids

Jardé, Thierry, Lloyd-Lewis, Bethan, Thomas, Mairian, Kendrick, Howard, Melchor, Lorenzo, Bougaret, Lauriane, Watson, Peter D., Ewan, Kenneth, Smalley, Matthew J. and Dale, Trevor Clive 2016. Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids. Nature Communications 7 , 13207. 10.1038/ncomms13207

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Publisher: Nature Publishing Group
ISSN: 2041-1723
Funders: Cancer Research UK, Breast Cancer Campaign, Marie Curie Intra European fund
Date of First Compliant Deposit: 31 October 2016
Date of Acceptance: 13 September 2016
Last Modified: 24 Apr 2019 12:24
URI: http://orca.cf.ac.uk/id/eprint/95695

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