Publications [#198259] of Gregory M Palmer

Papers Published

1. GM Palmer, Z Tiran, Z Zhou, ME Capozzi, W Park, C Coletta, A Pyriochou, Y Kliger, O Levy, I Borukhov, MW Dewhirst, G Rotman, JS Penn, A Papapetropoulos, A Novel Angiopoietin-derived Peptide Displays Anti-angiogenic Activity and Inhibits Tumor-induced and Retinal Neovascularization., British journal of pharmacology (September, 2011), ISSN 1476-5381 [doi]
   (last updated on 2011/12/01)

   Abstract:
   Background and purpose:  Pathological angiogenesis is associated with various human diseases, such as cancer, autoimmune diseases and retinopathy. The angiopoietin (Ang)-Tie2 system plays critical roles in multiple steps of the angiogenic remodeling process. In this study, we investigated the anti-angiogenic effect of a novel angiopoietin-derived peptide. Experimental approach:  Using computational methods, we identified peptides from helical segments within angiopoietins, which were predicted to inhibit their activity. These peptides were tested using biochemical methods and models of angiogenesis. The peptide with best efficacy, A11, was selected for further characterization as an anti-angiogenic compound. Key results:  The potent anti-angiogenic activity of A11 was demonstrated in a multicellular assay of angiogenesis and in the chorioallantoic membrane model. A11 bound to angiopoietins and reduced the binding of Ang-2 to Tie2. A11 was also found to significantly reduce vascular density in a model of tumor-induced angiogenesis. Its ability to inhibit Ang-2 but not Ang-1-induced endothelial cell migration, and to downregulate Tie2 levels in tumor microvessels, suggests that A11 targets the Ang-Tie2 pathway. Further evaluation of A11 in a rat model of oxygen-induced retinopathy, revealed a profound reduction of retinal angiogenesis. Moreover, combination of A11 with the anti-VEGF antibody demonstrated further inhibition of angiogenesis, implying an additive effect. Conclusions and Implications:  Taken together, our results indicate that A11 is a potent anti-angiogenic compound, which appears to exert its activity by modulating the Ang-Tie2 system, underlining its potential as a therapeutic agent for the treatment of ocular and tumor neovascularization, as well as other pathological conditions that are dependent on angiogenesis.