Reference : NF-kappaB activation in endothelial cells is critical for the activity of angiostatic...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/26000
NF-kappaB activation in endothelial cells is critical for the activity of angiostatic agents.
English
Tabruyn, Sébastien mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Memet, Sylvie [> > > >]
Ave, Patrick [> > > >]
Verhaeghe, Catherine mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Génétique générale et humaine >]
Mayo, Kevin H [> > > >]
Struman, Ingrid mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Martial, Joseph mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Griffioen, Arjan W [> > > >]
2009
Molecular Cancer Therapeutics
American Association for Cancer Research, Inc. (AACR)
8
9
2645-54
Yes (verified by ORBi)
International
1535-7163
1538-8514
Philadelphia
PA
[en] In tumor cells, the transcription factor NF-kappaB has been described to be antiapoptotic and proproliferative and involved in the production of angiogenic factors such as vascular endothelial growth factor. From these data, a protumorigenic role of NF-kappaB has emerged. Here, we examined in endothelial cells whether NF-kappaB signaling pathway is involved in mediating the angiostatic properties of angiogenesis inhibitors. The current report describes that biochemically unrelated agents with direct angiostatic effect induced NF-kappaB activation in endothelial cells. Our data showed that endostatin, anginex, angiostatin, and the 16-kDa N-terminal fragment of human prolactin induced NF-kappaB activation in endothelial cells in both cultured human endothelial cells and in vivo in a mouse tumor model. It was also found that NF-kappaB activity was required for the angiostatic activity, because inhibition of NF-kappaB in endothelial cells impaired the ability of angiostatic agents to block sprouting of endothelial cells and to overcome endothelial cell anergy. Therefore, activation of NF-kappaB in endothelial cells can result in an unexpected antitumor outcome. Based on these data, the current approach of systemic treatment with NF-kappaB inhibitors may therefore be revisited because NF-kappaB activation specifically targeted to endothelial cells might represent an efficient strategy for the treatment of cancer.
http://hdl.handle.net/2268/26000
10.1158/1535-7163.MCT-09-0383

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