title: Anti-angiogenic properties of ADAMTS-4 in vitro.
abstract: Angiogenesis is an indispensable mechanism in development and in many pathologies, including cancer, synovitis and aberrant wound healing. Many angiogenic stimulators and inhibitors have been investigated, and some have progressed to the clinic. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a group of multifunctional proteinases. ADAMTS-1 and ADAMTS-8 have been reported to be anti-angiogenic. Here, we provide evidence that ADAMTS-4, like ADAMTS-1, is expressed by endothelial cells and binds to vascular endothelial groth factor (VEGF). Moreover, ADAMTS-4 inhibited human dermal microvascular endothelial cells (HuDMEC) VEGF-stimulated VEGF receptor (R) R2 phosphorylation, differentiation and migration, suggesting that ADAMTS-4 may be a novel anti-angiogenic molecule.
authors.affiliation: Academic Unit of Molecular Medicine and Rheumatology, University of Sheffield Medical School, Sheffield, UK.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hsu
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Staton
authors.forename: Neil
authors.initials: N
authors.lastname: Cross
authors.forename: David J
authors.initials: DJ
authors.lastname: Buttle
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism* / Q000494:pharmacology*; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D020405:Dermis / Q000098:blood supply; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011348:Procollagen N-Endopeptidase / Q000378:metabolism* / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human