Abstract
The human CXC-chemokine CXCL4 is a potent inhibitor of tumor-induced angiogenesis. Considering that CXCL4 is sequestered in platelet α-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 αvβ3 on the surface of αvβ3-CHO. More importantly, human umbilical vein endothelial cells adhere to immobilized CXCL4 through αvβ3 integrin, and also through other integrins, such as αvβ5 and α5β1. 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.
Highlights
Angiogenesis is the formation of new capillaries from preexisting blood vessels
Taking into account that CXCL4 is released from the agranules of activated platelets in the vicinity of vessel wall injury [18] and that CXCL4 targets the endothelial cells in vivo that undergo active angiogenesis [19,20], we examined the possibility that CXCL4 might function as a ligand for integrins
We sought to assess whether CXCL4, a CXC chemokine that exhibit potent anti-angiogenic activities, and its C-terminus derived peptide CXCL4/CTF, would function as ligands for the integrin receptors on the surface of endothelial cells
Summary
Angiogenesis is the formation of new capillaries from preexisting blood vessels. Angiogenesis plays an important role in physiologic processes such as wound healing and in disease progression such as cancer, diabetic retinopathy and various inflammatory disorders [1]. CXCL4 and the peptide derived from its carboxylterminal domain (CXCL4/CTF) display a strong antiangiogenic activity in vitro [5,6,7] and in vivo [5,7,8] They suppress growth of various tumors [9,10,11] and metastasis [12] in vivo. Integrins are the major adhesion receptors used by endothelial cells undergoing angiogenesis to interact with their extracellular matrix (ECM). This interaction causes spreading of endothelial cells with cytoskeleton re-organization events necessary for cells to invade ECM, to proliferate, to migrate and to form new tubular vessels [13]. Taken together with the established importance of integrin in tumor angiogenesis, this study provides a new mechanistic context for the function of CXCL4 as an angiogenesis inhibitor
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
