Inhibition of tissue factor activity reduces the density of cellular network formation in an in vitro model of angiogenesis.
Tissue factor (TF) is a transmembrane glycoprotein that was originally recognized for its ability to initiate the extrinsic pathway of coagulation. More recently, additional functions of TF in cellular signalling have emerged, notably the role of TF in vasculogenesis and angiogenesis. We have described previously the ability of a peptide derived from the apolipoprotein B100 (apoB100) moiety of low-density lipoproteins (KRAD14) to inhibit the procoagulant function of TF. In this study, we demonstrate the ability of the KRAD14 peptide to attenuate the density of cellular network structures of T24 cells grown on specialized matrix (Matrigel). In addition, an alternative inhibitor of TF activity, the TF8 5G9 antibody, also reduces the density of cellular network formation. Targeted use of a stable structural equivalent of the KRAD14 peptide may thus prove useful in the prophylactic treatment of diseases whose pathologies feature the formation of neovascular tissue, e.g. tumour growth and metastasis, rupture of atherosclerotic plaques and retinopathy secondary to diabetes.
James
N J
NJ
Department of Biochemistry and Molecular Biology, Royal Free and University College Medical Schools, Rowland Hill Street, Hampstead, London NW3 2PF, U.K. nickie@njce.fsnet.co.uk
Ettelaie
C
C
Bruckdorfer
K R
KR
D000595:Amino Acid Sequence; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D015942:Factor VIIa / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D009389:Neovascularization, Pathologic / Q000503:physiopathology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000188:drug therapy
D000906:Antibodies; D010446:Peptide Fragments; D013925:Thromboplastin; D015942:Factor VIIa