Cancer Letters, Oct 28, 2010, Vol.296(2), p.160(8)
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.canlet.2010.04.010 Byline: Wolf-Dietrich C. Beecken (a), Eva Maria Ringel (a), Jan Babica (b), Elsie Oppermann (c), Dietger Jonas (a), Roman A. Blaheta (a) Keywords: Angiogenesis; [beta].sub.2-Glycoprotein-I; Cell cycle; Cyclins; HUVEC Abstract: [beta].sub.2-Glycoprotein-I ([beta].sub.2gpI), an abundant plasma glycoprotein, functions as a regulator of thrombosis. Previously, we demonstrated that plasmin-clipped [beta].sub.2gpI (c[beta].sub.2gpI) exerts an anti-angiogenic effect on human umbilical vein endothelial cells (HUVEC). The present study was focused on the molecular background responsible for this phenomenon. c[beta].sub.2gpI strongly reduced HUVEC growth and proliferation as evidenced by the MTT and BrdU assay and delayed cell cycle progression arresting HUVEC in the S-and G2/M-phase. Western blot analysis indicated that c[beta].sub.2gpI inhibited cyclin A, B and D1, and enhanced p21 and p27 expression. Activity of p38 was down-regulated independently from the c[beta].sub.2gpI incubation time. Phosphorylation of ERK1/2 was not changed early (30 and 60min) but became enhanced later (90min, 4h). JNK activity was reduced rapidly after c[beta].sub.2gpI treatment but compared to controls, increased thereafter. Annexin II blockade prevented growth inhibition and cell cycle delay evoked by c[beta].sub.2gpI. We assume that c[beta].sub.2gpI's effects on HUVEC growth is mediated via cyclin A, B and D1 suppression, up-regulation of p21 and p27 and coupled to modifications of the mitogen-activated protein (MAP) kinase signalling pathway. c[beta].sub.2gpI may represent a potential endogenous angiogenesis-targeted compound, opening the possibility of a novel tool to treat cancer. Author Affiliation: (a) Department of Urology, J.W. Goethe-University, Frankfurt am Main, Germany (b) Institute of Biochemistry II, J.W. Goethe-University, Frankfurt am Main, Germany (c) Department of General and Visceral Surgery, J.W. Goethe-University, Frankfurt am Main, Germany Article History: Received 3 September 2009; Revised 19 March 2010; Accepted 6 April 2010
Endothelium -- Growth ; Endothelium -- Analysis
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