Angiostatic and chemotactic activities of the CXC chemokine CXCL4L1 (platelet factor-4 variant) are mediated by CXCR3
Open Access
- 12 January 2011
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 117 (2), 480-488
- https://doi.org/10.1182/blood-2009-11-253591
Abstract
We investigated possible cellular receptors for the human CXC chemokine platelet factor-4 variant/CXCL4L1, a potent inhibitor of angiogenesis. We found that CXCL4L1 has lower affinity for heparin and chondroitin sulfate-E than platelet factor-4 (CXCL4) and showed that CXCL10 and CXCL4L1 could displace each other on microvascular endothelial cells. Labeled CXCL4L1 also bound to CXCR3A- and CXCR3B-transfectants and was displaced by CXCL4L1, CXCL4, and CXCL10. The CXCL4L1 anti-angiogenic activity was blocked by anti-CXCR3 antibodies (Abs) in the Matrigel and cornea micropocket assays. CXCL4L1 application in CXCR3(-/-) or in wild-type mice treated with neutralizing anti-CXCR3 Abs, resulted in reduced inhibitory activity of CXCL4L1 on tumor growth and vascularization of Lewis lung carcinoma. Furthermore, CXCL4L1 and CXCL4 chemoattracted activated T cells, human natural killer cells, and human immature dendritic cells (DCs). Migration of DCs toward CXCL4 and CXCL4L1 was desensitized by preincubation with CXCL10 and CXCL11, inhibited by pertussis toxin, and neutralized by anti-CXCR3 Abs. Chemotaxis of T cells, natural killer cells, and DCs is likely to contribute to the antitumoral action. However, the in vivo data indicate that the angiostatic property of CXCL4L1 is equally important in retarding tumor growth. Thus, both CXCR3A and CXCR3B are implicated in the chemotactic and vascular effects of CXCL4L1. (Blood. 2011; 117(2):480-488)Keywords
This publication has 48 references indexed in Scilit:
- Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14Blood, 2009
- Calcineurin Inhibitors Modulate CXCR3 Splice Variant Expression and Mediate Renal Cancer ProgressionJournal of the American Society of Nephrology, 2008
- CXC and CC Chemokines Form Mixed HeterodimersPublished by Elsevier BV ,2008
- Inhibition of Gαi2 Activation by Gαi3 in CXCR3-mediated SignalingPublished by Elsevier BV ,2007
- A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor developmentThe Journal of Experimental Medicine, 2006
- CXC chemokines in angiogenesisCytokine & Growth Factor Reviews, 2005
- Dendritic cell trafficking: More than just chemokinesCytokine & Growth Factor Reviews, 2005
- Regulation of the trafficking of tumour-infiltrating dendritic cells by chemokinesSeminars in Cancer Biology, 2004
- Molecular characterization of the chemokine receptor CXCR3: evidence for the involvement of distinct extracellular domains in a multi‐step model of ligand binding and receptor activationEuropean Journal of Immunology, 2003
- Inhibition of Angiogenesis by Recombinant Human Platelet Factor-4 and Related PeptidesScience, 1990