Mechanostimulation of breast myoepithelial cells induces functional changes associated with DCIS progression to invasion

Hayward, Mary-Kate, Allen, Michael D., Gomm, Jennifer J., Goulding, Iain, Thompson, Clare L., Knight, Martin M., Marshall, John F. and Jones, J. Louise (2022) Mechanostimulation of breast myoepithelial cells induces functional changes associated with DCIS progression to invasion. npj Breast Cancer, 8. ISSN 2374-4677

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Abstract

Women with ductal carcinoma in situ (DCIS) have an increased risk of progression to invasive breast cancer. Although not all women with DCIS will progress to invasion, all are treated as such, emphasising the need to identify prognostic biomarkers. We have previously shown that altered myoepithelial cells in DCIS predict disease progression and recurrence. By analysing DCIS duct size in sections of human breast tumour samples, we identified an associated upregulation of integrin β6 and an increase in periductal fibronectin deposition with increased DCIS duct size that associated with the progression of DCIS to invasion. Our modelling of the mechanical stretching myoepithelial cells undergo during DCIS progression confirmed the upregulation of integrin β6 and fibronectin expression in isolated primary and cell line models of normal myoepithelial cells. Our studies reveal that this mechanostimulated DCIS myoepithelial cell phenotype enhances invasion in a TGFβ-mediated upregulation of MMP13. Immunohistochemical analysis identified that MMP13 was specifically upregulated in DCIS, and it was associated with progression to invasion. These findings implicate tissue mechanics in altering the myoepithelial cell phenotype in DCIS, and that these alterations may be used to stratify DCIS patients into low and high risk for invasive progression.

Item Type: Article
Additional Information: Funding Information: The authors wish to acknowledge the role of the Breast Cancer Now Tissue Bank in collecting and making available the samples used in the generation of this publication, and all the patients who donated. We also thank the BCI pathology core for tissue processing and the BCI flow cytometry core for machine assistance. This work was supported by the Pathological Society of Great Britain and Ireland PhD studentship, the Breast Cancer Now Tissue Bank Cell Culture Programme, a Cancer Research UK (CRUK) Core Service Grant (C16420/A18066) and a CRUK Centre Grant to BCI (C355/A25137). Publisher Copyright: © 2022, Crown.
Uncontrolled Keywords: oncology,radiology nuclear medicine and imaging,pharmacology (medical),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2730
Faculty \ School:
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 03 Nov 2022 10:30
Last Modified: 06 Jun 2024 15:20
URI: https://ueaeprints.uea.ac.uk/id/eprint/89541
DOI: 10.1038/s41523-022-00464-4

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