ArticleBreast cancer research : BCR2017
Loss of MMP-8 in ductal carcinoma in situ (DCIS)-associated myoepithelial cells contributes to tumour promotion through altered adhesive and proteolytic function.
Article in Breast cancer research : BCR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- The Role of MMP8 in Cancer: A Systematic Review.International journal of molecular sciences · 2019Pooled it
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- The Microenvironment in DCIS and Its Role in Disease Progression.Advances in experimental medicine and biology · 2025Review
- From ductal carcinoma in situ to invasive breast cancer: the prognostic value of the extracellular microenvironment.Journal of experimental & clinical cancer research : CR · 2024Review
- Review
- Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance.Signal transduction and targeted therapy · 2024Review
- Chromatin insulation orchestrates matrix metalloproteinase gene cluster expression reprogramming in aggressive breast cancer tumors.Molecular cancer · 2023Article
- Computational design of matrix metalloprotenaise-9 (MMP-9) resistant to auto-cleavage.The Biochemical journal · 2023Article
- Designed Loop Extension Followed by Combinatorial Screening Confers High Specificity to a Broad Matrix MetalloproteinaseInhibitor.Journal of molecular biology · 2023Article
- Article
- The Variety of 3D Breast Cancer Models for the Study of Tumor Physiology and Drug Screening.International journal of molecular sciences · 2023Review
- Computational design of Matrix Metalloprotenaise-9 (MMP-9) resistant to auto-cleavage.bioRxiv : the preprint server for biology · 2023Article
- TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression.NPJ breast cancer · 2023Article
- Dedifferentiation-mediated stem cell niche maintenance in early-stage ductal carcinoma in situ progression: insights from a multiscale modeling study.Cell death & disease · 2022Article
- MMP8 increases tongue carcinoma cell-cell adhesion and diminishes migration via cleavage of anti-adhesive FXYD5.Oncogenesis · 2021Article
- Article
- Interleukin-6-mediated epigenetic control of the VEGFR2 gene induces disorganized angiogenesis in human breast tumors.The Journal of biological chemistry · 2020Article
- Loss of myoepithelial calponin-1 characterizes high-risk ductal carcinoma in situ cases, which are further stratified by T cell composition.Molecular carcinogenesis · 2020Article
- Breaking through to the Other Side: Microenvironment Contributions to DCIS Initiation and Progression.Journal of mammary gland biology and neoplasia · 2018Review
- The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNormal myoepithelial cells (MECs) play an important tumour-suppressor role in the breast but display an altered phenotype in ductal carcinoma in situ (DCIS), gaining tumour-promoter functions. Matrix metalloproteinase-8 (MMP-8) is expressed by normal MECs but is lost in DCIS. This study investigated the function of MMP-8 in MECs and the impact of its loss in DCIS.
methodsPrimary normal and DCIS-associated MECs, and normal (N-1089) and DCIS-modified myoepithelial (β6-1089) cell lines, were used to assess MMP-8 expression and function. β6-1089 lacking MMP-8 were transfected with MMP-8 WT and catalytically inactive MMP-8 EA, and MMP-8 in N-1089 MEC was knocked down with siRNA. The effect on adhesion and migration to extracellular matrix (ECM), localisation of α6β4 integrin to hemidesmosomes (HD), TGF-β signalling and gelatinase activity was measured. The effect of altering MEC MMP-8 expression on tumour cell invasion was investigated in 2D and 3D organotypic models.
resultsAssessment of primary cells and MEC lines confirmed expression of MMP-8 in normal MEC and its loss in DCIS-MEC. Over-expression of MMP-8 WT but not MMP-8 EA in β6-1089 cells increased adhesion to ECM proteins and reduced migration. Conversely, knock-down of MMP-8 in N-1089 reduced adhesion and increased migration. Expression of MMP-8 WT in β6-1089 led to greater localisation of α6β4 to HD and reduced retraction fibre formation, this being reversed by MMP-8 knock-down in N-1089. Over-expression of MMP-8 WT reduced TGF-β signalling and gelatinolytic activity. MMP-8 knock-down enhanced TGF-β signalling and gelatinolytic activity, which was reversed by blocking MMP-9 by knock-down or an inhibitor. MMP-8 WT but not MMP-8 EA over-expression in β6-1089 reduced breast cancer cell invasion in 2D and 3D invasion assays, while MMP-8 knock-down in N-1089 enhanced cancer cell invasion. Staining of breast cancer cases for MMP-8 revealed a statistically significant loss of MMP-8 expression in DCIS with invasion versus pure DCIS (p = 0.001).
conclusionsThese data indicate MMP-8 is a vital component of the myoepithelial tumour-suppressor function. It restores MEC interaction with the matrix, opposes TGF-β signalling and MMP-9 proteolysis, which contributes to inhibition of tumour cell invasion. Assessment of MMP-8 expression may help to determine risk of DCIS progression.
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