Article (Scientific journals)
Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors.
Maquoi, Erik; Munaut, Carine; Colige, Alain et al.
2002In Experimental Cell Research, 275 (1), p. 110-21
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Keywords :
Collagen Type IV/pharmacology; transcriptional regulation; plasminogen; MMP inhibitor; proteolysis; invasion; tumor; Enzyme Activation; Fibrosarcoma/enzymology/pathology; Humans; Interleukin-1/pharmacology; Interleukin-1beta; Matrix Metalloproteinase 9/antagonists & inhibitors/biosynthesis/drug effects/metabolism; Matrix Metalloproteinases/antagonists & inhibitors; Neoplasm Invasiveness; Peptide Fragments/pharmacology; Phenylalanine/analogs & derivatives/pharmacology; Transcription, Genetic; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha/pharmacology
Abstract :
[en] Enhanced expression and activation of matrix metalloproteinase-2 (MMP-2) and MMP-9 have been associated with tumor progression, invasion, and metastasis. The use of synthetic MMP inhibitors to block the proteolytic activity of these enzymes recently emerged as a potential therapeutic tool to treat cancer. In this study, we report that GI129471, a synthetic broad-spectrum MMP inhibitor, efficiently reduced the in vitro invasiveness of HT1080 cells through type IV collagen, a major component of basement membranes. This reduced invasion was paralleled by a complete inhibition of pro-MMP-2 activation; however, GI129471 strongly increased the amount of secreted pro-MMP-9, which could be subsequently activated through a plasminogen-dependent mechanism. Quantitative RT-PCR and northern blot analysis revealed that GI129471 specifically increased the MMP-9 mRNA steady-state level. Moreover, transient transfection of HT1080 cells with beta-galactosidase reporter vectors containing different lengths of the 5'-flanking region of the MMP-9 gene revealed an upregulation of the transcriptional activity of the corresponding promoter. Well-known modulators of MMP-9 expression such as Il-1beta and TNF-alpha were not involved in this upregulation. These findings emphasize the complexity of the regulation of MMP expression and the requirement for a detailed characterization of the potential adverse side effects associated with the use of broad-spectrum MMPIs.
Disciplines :
Oncology
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Maquoi, Erik  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Munaut, Carine  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Colige, Alain ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Lambert, Charles ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Frankenne, Francis
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Grams, Frank
Krell, Hans-Willi
Foidart, Jean-Michel ;  Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Language :
English
Title :
Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors.
Publication date :
2002
Journal title :
Experimental Cell Research
ISSN :
0014-4827
eISSN :
1090-2422
Publisher :
Academic Press, Orlando, United States - Florida
Volume :
275
Issue :
1
Pages :
110-21
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright 2002 Elsevier Science (USA).
Available on ORBi :
since 07 May 2009

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