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Regulation of matrix metalloproteinase-2(gelatinase A, MMP-2), membrane-type matrixmetalloproteinase-1 (MT1-MMP) and tissue inhibitorof metalloproteinases-2 (TIMP-2) expression byelastin-derived peptides in human HT-1080 fibrosarcoma cell line

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Abstract

Soluble kappa-elastin peptides were shown to stimulate the expression of MMP-2 (but not MMP-9) byhuman fibrosarcoma HT-1080 cells, both at the protein and mRNA levels; maximal effect being observedat a concentration of 25 mg/ml of kappa-elastin. The stimulatory effect could be reproduced using Val-Gly-Val-Ala-Pro-Gly (VGVAPG) peptide, an elastin-derived hydrophobic hexapeptide which represented theelastin receptor binding sequence of tropoelastin. Furthermore, treatment of cells with lactose (30 mM),which dissociated 67-kDa elastin binding protein (EBP) from cell surfaces, completely abolished this effect,suggesting that the elastin receptor could mediate such a response. Using a specific monoclonal antibody,67-kDa EBP was detected in HT-1080 membrane preparations by Western immunoblotting. Following treat-mentwith 25 mg/ml kappa-elastin or 200 mg/ml VGVAPG, increased levels of the active 62-kDa form ofMMP-2 were found in HT-1080 cell extracts. Stimulation of MT1-MMP mRNA expression by treatmentwith elastin-derived peptides (EDPs) was shown by competitive polymerase chain reaction (PCR). A reversezymography analysis revealed that EDPs also stimulated TIMP-2 (but not TIMP-1) production by HT-1080cells. Competitive PCR confirmed increased TIMP-2 mRNA expression by such treatment. These resultssuggest that occupancy of the 67-kDa elastin receptor by elastin-derived peptides enhanced both expressionand activation of proMMP-2 and consequently, could promote the invasive/metastatic ability of tumor cellsexpressing this receptor. ©Kluwer Academic Publishers

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  1. Laboratoire de Biochimie, CNRS, Faculte de Medecine Reims, Upresa 6021, IFR 53-Biomo Pailes, France

    Bertrand Brassart, Alain Randoux, William Hornebeck & Herv Emonard

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  1. Bertrand Brassart
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  2. Alain Randoux
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Brassart, B., Randoux, A., Hornebeck, W. et al. Regulation of matrix metalloproteinase-2(gelatinase A, MMP-2), membrane-type matrixmetalloproteinase-1 (MT1-MMP) and tissue inhibitorof metalloproteinases-2 (TIMP-2) expression byelastin-derived peptides in human HT-1080 fibrosarcoma cell line. Clin Exp Metastasis 16, 489–500 (1998). https://doi.org/10.1023/A:1006550503612

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