Stromelysin-2 (Matrix Metalloproteinase 10) Is Inducible in Lymphoma Cells and Accelerates the Growth of Lymphoid Tumors In Vivo
Autor: | Yves St-Pierre, Edouard F. Potworowski, Tommy Alain, Céline Van Themsche, Anna E. Kossakowska, Stefan J. Urbanski |
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Rok vydání: | 2004 |
Předmět: |
Male
Lymphoma B-Cell CD30 MMP10 Immunology Biology Lymphoma T-Cell Cell Line Proinflammatory cytokine Extracellular matrix Mice Matrix Metalloproteinase 10 Cell Line Tumor hemic and lymphatic diseases medicine Animals Humans Immunology and Allergy Neoplasm Invasiveness Thymic Lymphoma Metalloendopeptidases Intercellular Adhesion Molecule-1 medicine.disease Lymphocyte Function-Associated Antigen-1 BCL10 Up-Regulation Lymphoma Gene Expression Regulation Neoplastic Mice Inbred C57BL Cell culture Enzyme Induction Hemangioendothelioma Cancer research Cytokines Female Cell Division Neoplasm Transplantation |
Zdroj: | The Journal of Immunology. 173:3605-3611 |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.173.6.3605 |
Popis: | Matrix metalloproteinase (MMP) 10 (stromelysin-2) is known to degrade various components of the extracellular matrix; however, the signals that regulate its expression and its role in lymphoma growth remain unknown. In the present work, we report the up-regulated expression of MMP10 in T lymphoma cells following contact with endothelial cells. The induction of MMP10 was found to be dependent on the specific interaction between LFA-1 and ICAM-1, which play a central role in regulating the expression of genes involved in the rate-limiting steps of lymphoma development. MMP10, but not MMP3 (stromelysin-1), was also up-regulated in human B lymphoma cells following exposure to IL-4, IL-6, and IL-13, but not to IL-1. To gain further insight into the role of MMP10 in lymphoma development, we generated lymphoma cell lines constitutively expressing high levels of MMP10 and studied these cells for their ability to form thymic lymphoma in vivo. Mice injected with lymphoma cells constitutively expressing MMP10 developed thymic lymphoma more rapidly than those injected with control lymphoma cells. These results provide the first in vivo evidence that overexpression of MMP10 promotes tumor development, and indicate that MMP10 induction is an important pathway activated not only upon ICAM-1/LFA-1-mediated intercellular contact, but also following activation of tumor cells with inflammatory cytokines. |
Databáze: | OpenAIRE |
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