Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4- mediated tumor cell transendothelial migration by CXCR7 ligands

Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4- mediated tumor cell transendothelial migration by CXCR7 ligands
Authors Brian A Zabel, Yu Wang, Susanna Lewén, Robert D Berahovich, Mark ET Penfold, Penglie Zhang, Jay Powers, Bretton C Summers, Zhenhua Miao, Bin Zhao, Ali Jalili, Anna Janowska-Wieczorek, Juan C Jaen, Thomas J Schall
Publication date 2009/9/1
Journal The Journal of Immunology
Volume 183
Issue 5
Pages 3204-3211
Publisher American Association of Immunologists
Description CXCR7 binds chemokines CXCL11 (I-TAC) and CXCL12 (SDF-1) but does not act as a classical chemoattractant receptor. Using CCX771, a novel small molecule with high affinity and selectivity for CXCR7, we found that, although CXCR7 is dispensable for “bare filter” in vitro chemotaxis, CXCR7 plays an essential role in the CXCL12/CXCR4- mediated transendothelial migration (TEM) of CXCR4+ CXCR7+ human tumor cells. Importantly, although CXCL11 is unable to stimulate directly the migration of these cells, it acts as a potent antagonist of their CXCL12-induced TEM. Furthermore, even though this TEM is driven by CXCR4, the CXCR7 ligand CCX771 is substantially more potent at inhibiting it than the CXCR4 antagonist AMD3100, which is more than 100 times weaker at inhibiting TEM when compared with its ability to block bare filter chemotaxis. Far from being a “silent” receptor, we show that CXCR7 …
Total citations Cited by 321
Scholar articles Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4-mediated tumor cell transendothelial migration by CXCR7 ligands
BA Zabel, Y Wang, S Lewén, RD Berahovich… – The Journal of Immunology, 2009 Cited by 321 Related articles All 7 versions