Analysis of the impact of angiopoietin-like protein-3 and -4 stimulation on angiopoietin-2-induced signaling

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Angiopoietin-like proteins-3 and -4 (ANGPTL-3 and -4) are structurally similar with Angiopoietin-2 (Ang-2) protein but do not bind the Ang-2 receptor Tie2. Instead, ANGPTL-3 and -4 and Ang-2 protein bind the same angiogenic integrins (alphavbeta3-, alphavbeta5- und alphabeta1). In preliminary data, the applicant could demonstrate that ANGPTL-3 and -4 molecules and Ang-2 protein show similar binding sites (extracellular), both induce activation of the same integrin signaling pathway (FAK) and have similar effects in angiogenic endothelial cells (sprouting). If these observations are important for Anti-Ang-2 treatment has to be clarified. Consequently, this study aims to analyze if I.) ANGPTL-3 and -4 can replace Ang-2-incuded signaling and function and ii.) if this is of therapeutic relevance (determined exemplary in malignant melanoma).