Role of metalloproteinases MMP-9 and MT1-MMP in CXCL12-promoted myeloma cell invasion across basement membranes
| Autor: | Xonia Carvajal-Vergara, Salomón Matías-Román, Joaquin Teixidó, Isabel Molina-Ortiz, Atanasio Pandiella, Marisa Parmo-Cabañas, Inmaculada Valle, David García-Bernal, Alicia G. Arroyo |
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| Rok vydání: | 2005 |
| Předmět: |
Pathology
medicine.medical_specialty Stromal cell Matrix Metalloproteinases Membrane-Associated Cell Biocompatible Materials Biology Matrix metalloproteinase Basement Membrane Collagen Type I Pathology and Forensic Medicine Extracellular matrix Cell Movement Cell Line Tumor medicine Humans Neoplasm Invasiveness Multiple myeloma Basement membrane Matrigel Tissue Inhibitor of Metalloproteinase-1 medicine.disease Chemokine CXCL12 Matrix Metalloproteinases Extracellular Matrix Neoplasm Proteins Gene Expression Regulation Neoplastic Drug Combinations medicine.anatomical_structure Matrix Metalloproteinase 9 embryonic structures Cancer research Proteoglycans Collagen Laminin Bone marrow Stromal Cells Multiple Myeloma Chemokines CXC |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1096-9896 0022-3417 |
| DOI: | 10.1002/path.1876 |
| Popis: | Malignant plasma cells in multiple myeloma home to the bone marrow (BM), accumulate in different niches and, in late disease, migrate from the BM into blood. These migratory events involve cell trafficking across extracellular matrix (ECM)-rich basement membranes and interstitial tissues. Metalloproteinases (MMP) degrade ECM and facilitate tumour cell invasion. The chemokine CXCL12 is expressed in the BM, and it was previously shown that it triggers myeloma cell migration and activation. In the present work we show that CXCL12 promotes myeloma cell invasion across Matrigel-reconstituted basement membranes and type I collagen gels. MMP-9 activity was required for invasion through Matrigel towards CXCL12, whereas TIMP-1, a MMP-9 inhibitor that we found to be expressed by myeloma and BM stromal cells, impaired the invasion. In addition, we show that the membrane-bound MT1-MMP metalloproteinase is expressed by myeloma cells and contributes to CXCL12-promoted myeloma cell invasion across Matrigel. Increase in MT1-MMP expression, as well as induction of its membrane polarization by CXCL12 in myeloma cells, might represent potential mechanisms contributing to this invasion. CXCL12-promoted invasion across type I collagen involved metalloproteinases different from MT1-MMP. These data indicate that CXCL12 could contribute to myeloma cell trafficking in the BM involving MMP-9 and MT1-MMP activities. This work was supported by Grants G03/136 from Ministerio de Sanidad y Consumo (to J.T and A.P) and SAF2002-00068 from Ministerio de Educación y Ciencia (to A.G.A). |
| Databáze: | OpenAIRE |
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