Article (Scientific journals)
NF-kappaB activation in endothelial cells is critical for the activity of angiostatic agents.
Tabruyn, Sébastien; Memet, Sylvie; Ave, Patrick et al.
2009In Molecular Cancer Therapeutics, 8 (9), p. 2645-54
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Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Tabruyn, Sébastien ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Memet, Sylvie
Ave, Patrick
Verhaeghe, Catherine ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique générale et humaine
Mayo, Kevin H
Struman, Ingrid  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Martial, Joseph ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Griffioen, Arjan W
Language :
English
Title :
NF-kappaB activation in endothelial cells is critical for the activity of angiostatic agents.
Publication date :
2009
Journal title :
Molecular Cancer Therapeutics
ISSN :
1535-7163
eISSN :
1538-8514
Publisher :
American Association for Cancer Research, Inc. (AACR), Philadelphia, United States - Pennsylvania
Volume :
8
Issue :
9
Pages :
2645-54
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 11 February 2010

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