The CXC-chemokine CXCL4 interacts with integrins implicated in angiogenesis.
The human CXC-chemokine CXCL4 is a potent inhibitor of tumor-induced angiogenesis. Considering that CXCL4 is sequestered in platelet alpha-granules and released following platelet activation in the vicinity of vessel wall injury, we tested the hypothesis that CXCL4 might function as a ligand for integrins. Integrins are a family of adhesion receptors that play a crucial role in angiogenesis by regulating early angiogenic processes, such as endothelial cell adhesion and migration. Here, we show that CXCL4 interacts with alphavbeta3 on the surface of alphavbeta3-CHO. More importantly, human umbilical vein endothelial cells adhere to immobilized CXCL4 through alphavbeta3 integrin, and also through other integrins, such as alphavbeta5 and alpha5beta1. We further demonstrate that CXCL4-integrin interaction is of functional significance in vitro, since immobilized CXCL4 supported endothelial cell spreading and migration in an integrin-dependent manner. Soluble CXCL4, in turn, inhibits integrin-dependent endothelial cell adhesion and migration. As a whole, our study identifies integrins as novel receptors for CXCL4 that may contribute to its antiangiogenic effect.
Aidoudi
Sallouha
S
INSERM, U920, Talence, France. salouaaidoudi@yahoo.fr
Bujakowska
Kinga
K
Kieffer
Nelly
N
Bikfalvi
Andreas
A
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002465:Cell Movement; D019743:Chemokines, CXC / Q000378:metabolism / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010978:Platelet Factor 4 / Q000378:metabolism / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000378:metabolism
D019743:Chemokines, CXC; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D016023:Integrins; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D010978:Platelet Factor 4