ORBi: Hajitou Amin - Down-Regulation of Vascular Endothelial Growth Factor by Tissue Inhibitor of Metalloproteinase-2: Effect on in Vivo Mammary Tumor Growth and Angiogenesis

Reference : Down-Regulation of Vascular Endothelial Growth Factor by Tissue Inhibitor of Metalloprot...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/13252

Title :	Down-Regulation of Vascular Endothelial Growth Factor by Tissue Inhibitor of Metalloproteinase-2: Effect on in Vivo Mammary Tumor Growth and Angiogenesis
Language :	English
Author, co-author :	Hajitou, Amin [> > > >]
	Sounni, Nor Eddine [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
	Devy, Laetitia [> > > >]
	Grignet-Debrus, Christine [Université de Liège - ULg > Services administratifs généraux > Protection et hygiène du travail (SUPHT) >]
	Lewalle, Jean-Marc [> > > >]
	Li, Hong [> > > >]
	Deroanne, Christophe [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal. >]
	Lu, He [> > > >]
	Colige, Alain [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal. >]
	Nusgens, Betty [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
	Frankenne, Francis [> >]
	Maron, Anne [> > > >]
	Yeh, Patrice [> > > >]
	Perricaudet, Michel [> > > >]
	Chang, Yawen [> > > >]
	Soria, Claudine [> > > >]
	Calberg-Bacq, Claire-Michelle [> > > >]
	Foidart, Jean-Michel [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
	Noël, Agnès [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Publication date :	15-Apr-2001
Journal title :	Cancer Research
Publisher :	American Association for Cancer Research, Inc. (AACR)
Volume :	61
Issue/season :	8
Pages :	3450-7
Audience :	International
ISSN :	0008-5472
e-ISSN :	1538-7445
City :	Baltimore
Country :	MD
Abstract :	[en] The tissue inhibitor of metalloproteinases-2 (TIMP-2) has at least two independent functions, i.e., regulation of matrix metalloproteinases and growth promoting activity. We investigated the effects of TIMP-2 overexpression, induced by retroviral mediated gene transfer, on the in vivo development of mammary tumors in syngeneic mice inoculated with EF43.fgf-4 cells. The EF43.fgf-4 cells established by stably infecting the normal mouse mammary EF43 cells with a retroviral expression vector for the fgf-4 oncogene, are highly tumorigenic and overproduce vascular endothelial growth factor (VEGF). Despite a promotion of the in vitro growth rate of EF43.fgf-4 cells overexpressing timp-2, the in vivo tumor growth was delayed. At day 17 post-cell injection, the volume of tumor derived from TIMP-2-overexpressing cells was reduced by 80% as compared with that obtained with control cells. Overexpression of TIMP-2 was associated with a down-regulation of VEGF expression in vitro and in vivo, a reduction of vessel size, density, and blood supply in the induced tumors. In addition, TIMP-2 completely inhibited the angiogenic activity of EF43.fgf-4 cell-conditioned medium in vitro using a rat aortic ring model. Our findings suggest that overexpression of TIMP-2 delays growth and angiogenesis of mammary carcinoma in vivo and that down-regulation of VEGF expression may play an important role in this TIMP-2-mediated antitumoral and antiangiogenic effects. Finally the in vivo delivery of TIMP-2, as assessed by i.v. injection of recombinant adenoviruses vectors, significantly reduced the growth of the EF43.fgf-4-induced tumors. This effect of TIMP-2 was shown to be equally comparable with that of angiostatin, a known potent inhibitor of angiogenesis.
Permalink :	http://hdl.handle.net/2268/13252

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