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 ORCID: https://orcid.org/0000-0001-6622-9009, Smalley, Matthew J. ORCID: https://orcid.org/0000-0001-9540-1146 and Dale, Trevor C. ORCID: https://orcid.org/0000-0002-4880-9963 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:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Additional Information:	This work is licensed under a Creative Commons Attribution 4.0 International License.
Publisher:	Nature Research
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:	30 Jun 2023 18:19
URI:	https://orca.cardiff.ac.uk/id/eprint/95695

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