Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10
| Autor: | Jürgen Dittmer, Angela Dittmer, Jana Lützkendorf, Lutz P. Müller, Kristina Hohlfeld |
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| Rok vydání: | 2009 |
| Předmět: |
endocrine system
Pathology medicine.medical_specialty ADAM10 Active Transport Cell Nucleus Motility Breast Neoplasms Cellular and Molecular Neuroscience ADAM10 Protein Breast cancer Cell Movement Disintegrin medicine Cell Adhesion Tumor Cells Cultured Humans Cell adhesion Molecular Biology Pharmacology Mitogen-Activated Protein Kinase 3 biology Cadherin Mesenchymal stem cell Membrane Proteins Mesenchymal Stem Cells Cell Biology equipment and supplies medicine.disease Cadherins Coculture Techniques ADAM Proteins biology.protein Cancer research Molecular Medicine Amyloid Precursor Protein Secretases Breast carcinoma |
| Zdroj: | Cellular and molecular life sciences : CMLS. 66(18) |
| ISSN: | 1420-9071 |
| Popis: | Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs) on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied by a disruption of cell-cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage and enhanced migration. Our data suggest that hMSCs interfere with cell-cell adhesion and enhance migration of breast cancer cells by activating ADAM10. |
| Databáze: | OpenAIRE |
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