[en] Zoledronate exhibits antiangiogenic properties in vitro and in vivo. Integrins alpha v beta 3 and alpha v beta 5 are involved in angiogenesis. Because zoledronate inhibits endothelial cell adhesion, the authors explored the hypothesis that it could alter these integrins recruitment to focal adhesion sites. Human umbilical vein endothelial cells ( HUVECs) were treated with zoledronate or with mevalonate pathway intermediates geranylgeraniol ( GGOH) and farnesol (FOH). Zoledronate generated a significant decrease in alpha v beta 3 and alpha v beta 5 expression at HUVEC cell surface using flow cytometry and immunofluorescence. This inhibition was reversed by GGOH but not by FOH. Cells cotreated with zoledronate and GGOH were able to attach to vitronectin through alpha v beta 3 and alpha v beta 5, as confirmed by the use of specific function-blocking antibodies. The authors showed that zoledronate alters endothelial cell integrin-mediated adhesion. This effect is likely to contribute to the previously demonstrated antiangiogenic effect of zoledronate. Whether this mechanism of action also applies to metastatic tumor cells is under investigation.
Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases
Chaplet, Michael
Bonjean, Karine ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie - Cytologie - Département des sciences biomédicales et précliniques
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Language :
English
Title :
Zoledronate inhibits alpha v beta 3 and alpha v beta 5 integrin cell surface expression in endothelial cells
Publication date :
2007
Journal title :
Endothelium: Journal of Endothelial Cell Research
ISSN :
1062-3329
eISSN :
1029-2373
Publisher :
Taylor & Francis Inc, Philadelphia, United States - Pennsylvania
Volume :
14
Issue :
2
Pages :
123-130
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
METABRE
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] ULg FSR - Université de Liège. Fonds spéciaux pour la recherche [BE] EC - European Commission [BE]
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