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

Thierry Jardé (), Bethan Lloyd-Lewis, Mairian Thomas, Howard Kendrick, Lorenzo Melchor, Lauriane Bougaret, Peter D. Watson, Kenneth Ewan, Matthew J. Smalley and Trevor C. Dale ()
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Thierry Jardé: Cardiff School of Biosciences, Cardiff University
Bethan Lloyd-Lewis: Cardiff School of Biosciences, Cardiff University
Mairian Thomas: Cardiff School of Biosciences, Cardiff University
Howard Kendrick: European Cancer Stem Cell Research Institute, Cardiff School of Biosciences, Cardiff University
Lorenzo Melchor: Breast Cancer Now, Institute of Cancer Research
Lauriane Bougaret: Cardiff School of Biosciences, Cardiff University
Peter D. Watson: Cardiff School of Biosciences, Cardiff University
Kenneth Ewan: Cardiff School of Biosciences, Cardiff University
Matthew J. Smalley: European Cancer Stem Cell Research Institute, Cardiff School of Biosciences, Cardiff University
Trevor C. Dale: Cardiff School of Biosciences, Cardiff University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13207

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