[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.
Research center :
Giga-Cancer - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Maillard, Catherine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Bouquet, C.
Petitjean, Marie
Mestdagt, Mélanie ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Frau, E.
Jost, Maud
Masset, Anne ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Opolon, P. H.
Beerman, F.
Abitbol, M.
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Perricaudet, M.
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Reduction of brain metastases in plasminogen activator inhibitor-1-deficient mice with transgenic ocular tumors
Publication date :
2008
Journal title :
Carcinogenesis
ISSN :
0143-3334
eISSN :
1460-2180
Publisher :
Irl Press at Oxford University Press, Oxford, United Kingdom
Volume :
29
Issue :
11
Pages :
2236-2242
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.
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