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The Chemokine CXCL13 (BCA-1) Inhibits FGF-2 Effects on Endothelial Cells

https://doi.org/10.1006/bbrc.2001.5924Get rights and content

Abstract

Several chemokines, belonging to both the CXC and CC classes, act as positive or negative regulators of angiogenesis. We sought to investigate the role of CXCL13, B cell-attracting chemokine 1 (BCA-1), also known as B-lymphocyte chemoattractant (BLC), on endothelial cell functions. We tested the effect of CXCL13 on HUVEC chemotaxis and proliferation in the presence of fibroblast growth factor (FGF)-2 and found that such chemokine inhibits FGF-2-induced functions, while is not active by itself. To test whether other FGF-2-mediated biological activities may be affected, we evaluated the ability of CXCL13 to rescue HUVEC from starvation-induced apoptosis, as FGF-2 is a survival factor for endothelial cells, and found that CXCL13 partially inhibits such rescue. Multiple mechanisms may be responsible for these biological activities as CXCL13 displaces FGF-2 binding to endothelial cells, inhibits FGF-2 homodimerization, and induces the formation of CXCL13–FGF-2 heterodimers. Our data suggest that CXCL13 may modulate angiogenesis by interfering with FGF-2 activity.

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    Citation Excerpt :

    CXCR3 binding ELR− CXC chemokines have angiostatic activities and include platelet factor-4 (PF-4)/CXCL4, platelet factor-4 variant (PF-4var)/CXCL4L1, monokine induced by interferon-γ (Mig)/CXCL9, interferon-γ inducible protein-10 (IP-10)/CXCL10 and interferon-inducible T cell alpha chemoattractant (I-TAC)/CXCL11 [10,12]. Also B cell-attracting chemokine-1 (BCA-1)/CXCL13, which binds CXCR5, is an angiostatic ELR− CXC chemokine [22]. The first evidence that non-neoplastic cells might influence tumor formation and growth came from the field of inflammation.

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