ORBi: Maquoi Erik - Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors

Reference : Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synt...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Oncology
	To cite this reference:	http://hdl.handle.net/2268/12345

Title :	Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors
Language :	English
Author, co-author :	Maquoi, Erik [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
	Munaut, Carine [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
	Colige, Alain [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal. >]
	Lambert, Charles [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal. >]
	Frankenne, Francis [ > > ]
	Noël, Agnès [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
	Grams, F. [> > > >]
	Krell, H. W. [> > > >]
	Foidart, Jean-Michel [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
Publication date :	15-Apr-2002
Journal title :	Experimental Cell Research
Publisher :	Academic Press
Volume :	275
Issue/season :	1
Pages :	110-121
Peer reviewed :	Yes (verified by ORBi)
Audience :	International
ISSN :	0014-4827
e-ISSN :	1090-2422
City :	Orlando
Country :	FL
Keywords :	[en] tumor ; invasion ; proteolysis ; MMP inhibitor ; plasminogen ; transcriptional regulation
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. (C) 2002 Elsevier Science (USA).
Permalink :	http://hdl.handle.net/2268/12345
DOI :	10.1006/excr.2002.5489

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