Reference : Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by s...
Scientific journals : Article
Human health sciences : Oncology
Life sciences : Anatomy (cytology, histology, embryology...) & physiology
http://hdl.handle.net/2268/19512
Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors.
English
Maquoi, Erik mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Munaut, Carine mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Colige, Alain mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs >]
Lambert, Charles mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs >]
Frankenne, Francis [> > > >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Grams, Frank [> > > >]
Krell, Hans-Willi [> > > >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement >]
2002
Experimental Cell Research
Academic Press
275
1
110-21
Yes (verified by ORBi)
International
0014-4827
1090-2422
Orlando
FL
[en] 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
[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.
http://hdl.handle.net/2268/19512
also: http://hdl.handle.net/2268/12345
10.1006/excr.2002.5489
Copyright 2002 Elsevier Science (USA).

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