| Autor: |
Shayin V. Gibson, Elena Tomas Bort, Lucía Rodríguez-Fernández, Michael D. Allen, Jennifer J. Gomm, Iain Goulding, Ulrich auf dem Keller, Andrea Agnoletto, Cathrin Brisken, Barrie Peck, Angus J. Cameron, John F. Marshall, J. Louise Jones, Edward P. Carter, Richard P. Grose |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
npj Breast Cancer, Vol 9, Iss 1, Pp 1-15 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2374-4677 |
| DOI: |
10.1038/s41523-023-00513-6 |
| Popis: |
Abstract 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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