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TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. Virtually all women with DCIS are treated, despite evidence suggesting up to half would remain with stable, non-threatening, disease. Overtreatment thus presents a pressing issue in DCIS management. To understand...

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Autores principales: Gibson, Shayin V., Tomas Bort, Elena, Rodríguez-Fernández, Lucía, Allen, Michael D., Gomm, Jennifer J., Goulding, Iain, auf dem Keller, Ulrich, Agnoletto, Andrea, Brisken, Cathrin, Peck, Barrie, Cameron, Angus J., Marshall, John F., Jones, J. Louise, Carter, Edward P., Grose, Richard P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981685/
https://www.ncbi.nlm.nih.gov/pubmed/36864079
http://dx.doi.org/10.1038/s41523-023-00513-6
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author Gibson, Shayin V.
Tomas Bort, Elena
Rodríguez-Fernández, Lucía
Allen, Michael D.
Gomm, Jennifer J.
Goulding, Iain
auf dem Keller, Ulrich
Agnoletto, Andrea
Brisken, Cathrin
Peck, Barrie
Cameron, Angus J.
Marshall, John F.
Jones, J. Louise
Carter, Edward P.
Grose, Richard P.
author_facet Gibson, Shayin V.
Tomas Bort, Elena
Rodríguez-Fernández, Lucía
Allen, Michael D.
Gomm, Jennifer J.
Goulding, Iain
auf dem Keller, Ulrich
Agnoletto, Andrea
Brisken, Cathrin
Peck, Barrie
Cameron, Angus J.
Marshall, John F.
Jones, J. Louise
Carter, Edward P.
Grose, Richard P.
author_sort Gibson, Shayin V.
collection PubMed
description Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. Virtually all women with DCIS are treated, despite evidence suggesting up to half would remain with stable, non-threatening, disease. Overtreatment thus presents a pressing issue in DCIS management. To understand the role of the normally tumour suppressive myoepithelial cell in disease progression we present a 3D in vitro model incorporating both luminal and myoepithelial cells in physiomimetic conditions. We demonstrate that DCIS-associated myoepithelial cells promote striking myoepithelial-led invasion of luminal cells, mediated by the collagenase MMP13 through a non-canonical TGFβ – EP300 pathway. In vivo, MMP13 expression is associated with stromal invasion in a murine model of DCIS progression and is elevated in myoepithelial cells of clinical high-grade DCIS cases. Our data identify a key role for myoepithelial-derived MMP13 in facilitating DCIS progression and point the way towards a robust marker for risk stratification in DCIS patients.
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spelling pubmed-99816852023-03-04 TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression Gibson, Shayin V. Tomas Bort, Elena Rodríguez-Fernández, Lucía Allen, Michael D. Gomm, Jennifer J. Goulding, Iain auf dem Keller, Ulrich Agnoletto, Andrea Brisken, Cathrin Peck, Barrie Cameron, Angus J. Marshall, John F. Jones, J. Louise Carter, Edward P. Grose, Richard P. NPJ Breast Cancer Article Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. Virtually all women with DCIS are treated, despite evidence suggesting up to half would remain with stable, non-threatening, disease. Overtreatment thus presents a pressing issue in DCIS management. To understand the role of the normally tumour suppressive myoepithelial cell in disease progression we present a 3D in vitro model incorporating both luminal and myoepithelial cells in physiomimetic conditions. We demonstrate that DCIS-associated myoepithelial cells promote striking myoepithelial-led invasion of luminal cells, mediated by the collagenase MMP13 through a non-canonical TGFβ – EP300 pathway. In vivo, MMP13 expression is associated with stromal invasion in a murine model of DCIS progression and is elevated in myoepithelial cells of clinical high-grade DCIS cases. Our data identify a key role for myoepithelial-derived MMP13 in facilitating DCIS progression and point the way towards a robust marker for risk stratification in DCIS patients. Nature Publishing Group UK 2023-03-02 /pmc/articles/PMC9981685/ /pubmed/36864079 http://dx.doi.org/10.1038/s41523-023-00513-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gibson, Shayin V.
Tomas Bort, Elena
Rodríguez-Fernández, Lucía
Allen, Michael D.
Gomm, Jennifer J.
Goulding, Iain
auf dem Keller, Ulrich
Agnoletto, Andrea
Brisken, Cathrin
Peck, Barrie
Cameron, Angus J.
Marshall, John F.
Jones, J. Louise
Carter, Edward P.
Grose, Richard P.
TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
title TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
title_full TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
title_fullStr TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
title_full_unstemmed TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
title_short TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
title_sort tgfβ-mediated mmp13 secretion drives myoepithelial cell dependent breast cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981685/
https://www.ncbi.nlm.nih.gov/pubmed/36864079
http://dx.doi.org/10.1038/s41523-023-00513-6
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