The Calpastatin-Derived Calpain Inhibitor CP1B Reduces mRNA Expression of Matrix Metalloproteinase-2 and -9 and Invasion by Leukemic THP-1 Cells
| Autor: | Shirley Gil-Parrado, Michael Heidinger, Christian Ries, Marianne Jochum, Lourdes Ruiz-Heinrich, Oliver Popp |
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| Rok vydání: | 2003 |
| Předmět: |
Cell Survival
Clinical Biochemistry Matrix metalloproteinase Biochemistry Gene Expression Regulation Enzymologic Extracellular matrix Tumor Cells Cultured Humans Neoplasm Invasiveness THP1 cell line RNA Messenger Molecular Biology Glycoproteins Calpastatin Matrigel Leukemia biology Calcium-Binding Proteins Calpain Molecular biology Extracellular Matrix Cell biology Haematopoiesis Matrix Metalloproteinase 9 Cell culture biology.protein Matrix Metalloproteinase 2 Cell Division |
| Zdroj: | Biological Chemistry. 384 |
| ISSN: | 1431-6730 |
| Popis: | The ubiquitous proteases mu- and m-calpain are Ca(2+)-dependent cysteine endopeptidases. Besides involvement in a variety of physio(patho)logical processes, recent studies suggest a pivotal role of calpains in differentiation of hematopoietic cells and tumor cell invasion. However, the precise actions of calpains and their endogenous inhibitor, calpastatin, in these processes are only partially understood. Here we have studied the role of the calpain/calpastatin system in the invasion of leukemic cells under basal and differentiation-stimulating conditions. To further differentiate the human leukaemic cell line THP-1 (monocytic), the cells were treated for 24 hours with the differentiation-stimulating reagents phorbol 12-myristate 13-acetate (PMA) and dimethyl sulfoxide (DMSO). Macrophage- and granulocyte-like differentiation was confirmed by induction of vimentin expression as well as by microscopic and fluorescence-assisted cytometric analysis. Extracellular matrix (ECM) invasion of both the basal and differentiation-stimulated cells in a Matrigel assay was inhibited by pre-incubation of the cells with the specific calpain inhibitor CP1B for 24 hours. Inhibition of invasiveness correlated with decreased mRNA expression and secretion of the matrix metalloproteinases MMP-2 and MMP-9. In contrast, addition of CP1B only during the invasion process did neither influence transmigration nor MMP release. This is the first report showing that the calpain/calpastatin system mediates MMP-mRNA expression of the leukemic THP-1 cells and as a consequence their invasiveness. |
| Databáze: | OpenAIRE |
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