Reference : Reduction of brain metastases in plasminogen activator inhibitor-1-deficient mice with t...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/7188
Reduction of brain metastases in plasminogen activator inhibitor-1-deficient mice with transgenic ocular tumors
English
Maillard, Catherine [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Bouquet, C. [> >]
Petitjean, Marie [> >]
Mestdagt, Mélanie [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Frau, E. [> >]
Jost, Maud [> >]
Masset, Anne mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Opolon, P. H. [> >]
Beerman, F. [> >]
Abitbol, M. [> >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement >]
Perricaudet, M. [> >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
2008
Carcinogenesis
Irl Press at Oxford University Press
29
11
2236-2242
Yes (verified by ORBi)
International
0143-3334
1460-2180
Oxford
United Kingdom
[en] Plasminogen activator inhibitor-1 ; angiogenesis ; ocular tumor ; brain metastasis
[en] Plasminogen activator inhibitor-1 is known to play a paradoxical positive role in tumor angiogenesis, but its contribution to metastatic spread remains unclear. We studied the impact of PAI-1 deficiency in a transgenic mouse model of ocular tumors originating from retinal epithelial cells and leading to brain metastasis (TRP-1/SV40 Tag mice). PAI-1 deficiency did not affect primary tumor growth or vascularization, but was associated with a smaller number of brain metastases. Brain metastases were found to be differentially distributed between the two genotypes. PAI-1-deficient mice displayed mostly secondary foci expanding from local optic nerve infiltration, whereas wild-type animals displayed more disseminated nodules in the scissura and meningeal spaces. SuperArray GEArray analyses aiming to detect molecules potentially compensating for PAI-1 deficiency demonstrated an increase in fibroblast growth factor-1 (FGF-1) gene expression in primary tumors, which was confirmed by RT-PCR and western blotting. Our data provide the first evidence of a key role for PAI-1 in a spontaneous model of metastasis, and suggest that angiogenic factors, such as FGF-1, may be important for primary tumor growth and may compensate for the absence of PAI-1. They identify PAI-1 and FGF-1 as important targets for combined anti-tumor strategies.
Giga-Cancer
http://hdl.handle.net/2268/7188
10.1093/carcin/bgn204
FP7 ; 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
C Maillard Article soumis.pdfAuthor preprint1.81 MBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.