scholarly journals Enhanced membrane-type 1 matrix metalloproteinase expression by hyaluronan oligosaccharides in breast cancer cells facilitates CD44 cleavage and tumor cell migration

2012 ◽  
Vol 28 (5) ◽  
pp. 1808-1814 ◽  
Author(s):  
CHANG-I KUNG ◽  
CHENG-YI CHEN ◽  
CHIH-CHANG YANG ◽  
CHENG-YU LIN ◽  
TIEN-HUA CHEN ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Matrix Metalloproteinase ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Cell Migration ◽  
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

Interactions of breast cancer cells with the microenvironment of the human bone marrow

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22097-e22097
Author(s):  
T. Kaiser ◽  
G. Klein ◽  
E. Solomayer ◽  
D. Wallwiener ◽  
T. Fehm
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Breast Cancer Cells ◽  
Migration Assays

e22097 Background: Bone is one of the most favored sites for metastasis of breast cancer cells (BrCa) resulting in the formation of osteolytic and/or osteoblastic lesions. There is increasing evidence that the bone marrow (BM) microenvironment plays a pivotal role in modulating tumor cell homing to the bone, metastasis and progression. However, the molecular crosstalk between BrCa cells and the cellular and extracellular components of the bone marrow leading to osteotropism still remains a poorly characterized step in the metastatic process. Methods: Cell adhesion and migration assays using the invasive MDA-MB-231 and the noninvasive MCF7 BrCa cell lines were performed to investigate the impact of BM components on cellular functions of tumor cells. Results: Cell-matrix adhesion assays showed a strong and concentration-dependent attachment of BrCa cells to several extracellular matrix components present in the human bone marrow such as fibronectin, different laminin isoforms, collagens type I and IV or tenascin-C. Moreover, the BrCa cells attached avidly to the BM-derived primary osteoblasts, whereas the binding to stromal cells was significantly weaker. Notably, cell-cell adhesion experiments with primary osteoclasts revealed an anti-adhesive effect on tumor cell binding leading to no attachment activity of BrCa cells with the cell surface of primary osteoclasts. The influence of cellular components of the BM on tumor cell migration was analyzed by cell migration assays using conditioned media of osteoblasts, osteoclasts and stromal cells or a modified Transwell chamber technique. The migration assays with invasive MDA-MB-231 cells clearly showed that osteoblasts, but not osteoclasts or stromal cells released factors which led to a faster wound closure, suggesting an enhanced migratory ability of the metastatic tumor cells, whereas the migration of nonmetastatic MCF7 cells was unaffected. Conclusions: These data indicate that the crosstalk with osteoblasts affects both the adhesive and the migratory ability of BrCa cells favoring the bone colonization process. Furthermore, the presented experimental conditions may provide useful tools to study effects of antiresorptive drugs like bisphosphonates to improve therapeutic strategies for treatment metastatic bone disease. No significant financial relationships to disclose.

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