Reference : Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/14397
Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis.
English
El Hour, Mehdi [> > > >]
Moncada-Pazos, A. [> >]
Blacher, Silvia mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Masset, Anne [> > > >]
Cal, S. [> >]
Berndt, Sarah [> > > >]
Detilleux, Julien [> > > >]
Host, Laurent [> > > >]
Obaya, A. J. [> >]
Maillard, Catherine [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Lopez-Otin, C. [> >]
2010
Oncogene
Nature Publishing Group
29
20
3025-32
Yes (verified by ORBi)
International
0950-9232
1476-5594
Basingstoke
United Kingdom
[en] ADAMTS-12 ; angiogenesis ; tumor suppression
[en] ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in tissue remodeling and angiogenesis associated with physiological and pathological processes. To elucidate the in vivo functions of ADAMTS-12, we have generated a knockout mouse strain (Adamts12−/−) in which Adamts12 gene was deleted. The mutant mice had normal gestations and no apparent defects in growth, life span and fertility. By applying three different in vivo models of angiogenesis (malignant keratinocyte transplantation, Matrigel plug and aortic ring assays) to Adamts12−/− mice, we provide evidence for a protective effect of this host enzyme toward angiogenesis and cancer progression. In the absence of Adamts-12, both the angiogenic response and tumor invasion into host tissue were increased. Complementing results were obtained by using medium conditioned by cells overexpressing human ADAMTS-12, which inhibited vessel outgrowth in the aortic ring assay. This angioinhibitory effect of ADAMTS-12 was independent of its enzymatic activity as a mutated inactive form of the enzyme was similarly efficient in inhibiting endothelial cell sprouting in the aortic ring assay than the wild-type form. Altogether, our results show that ADAMTS-12 displays antiangiogenic properties and protect the host toward tumor progression.
http://hdl.handle.net/2268/14397
10.1038/onc.2010.49
FP7 ; 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.

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