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Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell migration
Author(s) -
Suchting Steven,
Heal Paul,
Tahtis Kiki,
Stewart Lorna M.,
Bicknell Roy
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-1991fje
Subject(s) - angiogenesis , microbiology and biotechnology , chemotaxis , biology , in vivo , slit , receptor , extracellular , endothelial stem cell , cell migration , axon guidance , in vitro , cancer research , biochemistry , neuroscience , genetics , axon
Roundabout receptors are molecular guidance molecules that function by interaction with Slit proteins to regulate axon guidance, neuronal migration, and leukocyte chemotaxis. We recently isolated a novel roundabout gene, called Robo4, which is restricted in expression to the endothelium, notably in areas of angiogenesis. The aim of this study was to use the soluble extracellular domain of Robo4 as a probe of function in angiogenesis and endothelial biology. Thus, the soluble extracellular domain of the receptor (Robo4Fc) showed diverse in vivo and in vitro activities including 1 ) inhibition of angiogenesis in vivo in the rodent subcutaneous sponge model, 2 ) inhibition of tube formation in the rat aortic ring assay, 3 ) inhibition of VEGF‐ and bFGF‐stimulated endothelial cell migration, and 4 ) inhibition of endothelial proliferation. To assess whether Robo4Fc was inhibiting Slit‐mediated effects, we determined whether Robo4 and Slit interact. Recombinant Slits‐1, ‐2, and ‐3 were shown by immunoprecipitation and BiaCore analysis to bind to Robo1 but not Robo4. Further study of the role of Robo4 in angiogenesis appears justified.