TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression.
Date
2023-03-02ICR Author
Author
Gibson, SV
Tomas Bort, E
Rodríguez-Fernández, L
Allen, MD
Gomm, JJ
Goulding, I
Auf dem Keller, U
Agnoletto, A
Brisken, C
Peck, B
Cameron, AJ
Marshall, JF
Jones, JL
Carter, EP
Grose, RP
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Science & Technology
Life Sciences & Biomedicine
Oncology
CARCINOMA IN-SITU
GROWTH-FACTOR REQUIREMENTS
HUMAN MAMMARY-GLAND
COLLAGENASE-3 EXPRESSION
ALPHA-V-BETA-6 INTEGRIN
TUMOR MICROENVIRONMENT
COLLECTIVE INVASION
EPITHELIAL-CELLS
ACTIVATION
DCIS
Research team
Endocrine control mechans
Language
eng
Date accepted
2023-02-15
License start date
2023-03-02
Citation
npj Breast Cancer, 2023, 9 (1), pp. 9 -
Publisher
NATURE PORTFOLIO