scholarly journals Dynamics of internalization and recycling of the prometastatic membrane type 4 matrix metalloproteinase (MT4-MMP) in breast cancer cells

FEBS Journal ◽  
2016 ◽  
Vol 283 (4) ◽  
pp. 704-722 ◽  
Author(s):  
Alice Truong ◽  
Cassandre Yip ◽  
Alexandra Paye ◽  
Silvia Blacher ◽  
Carine Munaut ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Membrane Type

scholarly journals Restricted expression of membrane type 1-matrix metalloproteinase by myofibroblasts adjacent to human breast cancer cells

2003 ◽  
Vol 105 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Christèle Bisson ◽  
Silvia Blacher ◽  
Myriam Polette ◽  
Jean-Frédéric Blanc ◽  
Florence Kebers ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Membrane Type

scholarly journals Pharmacoproteomics of a Metalloproteinase Hydroxamate Inhibitor in Breast Cancer Cells: Dynamics of Membrane Type 1 Matrix Metalloproteinase-Mediated Membrane Protein Shedding

2008 ◽  
Vol 28 (15) ◽  
pp. 4896-4914 ◽  
Author(s):  
Georgina S. Butler ◽  
Richard A. Dean ◽  
Eric M. Tam ◽  
Christopher M. Overall
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Breast Cancer Cells ◽  
Ectodomain Shedding ◽  
Drug Actions ◽  
Membrane Type

ABSTRACT Broad-spectrum matrix metalloproteinase (MMP) inhibitors (MMPI) were unsuccessful in cancer clinical trials, partly due to side effects resulting from limited knowledge of the full repertoire of MMP substrates, termed the substrate degradome, and hence the in vivo functions of MMPs. To gain further insight into the degradome of MMP-14 (membrane type 1 MMP) an MMPI, prinomastat (drug code AG3340), was used to reduce proteolytic processing and ectodomain shedding in human MDA-MB-231 breast cancer cells transfected with MMP-14. We report a quantitative proteomic evaluation of the targets and effects of the inhibitor in this cell-based system. Proteins in cell-conditioned medium (the secretome) and membrane fractions with levels that were modulated by the MMPI were identified by isotope-coded affinity tag (ICAT) labeling and tandem mass spectrometry. Comparisons of the expression of MMP-14 with that of a vector control resulted in increased MMP-14/vector ICAT ratios for many proteins in conditioned medium, indicating MMP-14-mediated ectodomain shedding. Following MMPI treatment, the MMPI/vehicle ICAT ratio was reversed, suggesting that MMP-14-mediated shedding of these proteins was blocked by the inhibitor. The reduction in shedding or the release of substrates from pericellular sites in the presence of the MMPI was frequently accompanied by the accumulation of the protein in the plasma membrane, as indicated by high MMPI/vehicle ICAT ratios. Considered together, this is a strong predictor of biologically relevant substrates cleaved in the cellular context that led to the identification of many undescribed MMP-14 substrates, 20 of which we validated biochemically, including DJ-1, galectin-1, Hsp90α, pentraxin 3, progranulin, Cyr61, peptidyl-prolyl cis-trans isomerase A, and dickkopf-1. Other proteins with altered levels, such as Kunitz-type protease inhibitor 1 and beta-2-microglobulin, were not substrates in biochemical assays, suggesting an indirect affect of the MMPI, which might be important in drug development as biomarkers or, in preclinical phases, to predict systemic drug actions and adverse side effects. Hence, this approach describes the dynamic pattern of cell membrane ectodomain shedding and its perturbation upon metalloproteinase drug treatment.

scholarly journals Membrane-Type 1 Matrix Metalloproteinase Expression Is Regulated by Zonula Occludens-1 in Human Breast Cancer Cells

2005 ◽  
Vol 65 (17) ◽  
pp. 7691-7698 ◽  
Author(s):  
Myriam Polette ◽  
Christine Gilles ◽  
Béatrice Nawrocki-Raby ◽  
Jouko Lohi ◽  
Walter Hunziker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Zonula Occludens ◽  
Zonula Occludens 1 ◽  
Membrane Type
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