Abstract 3799: Urokinase kringle-derived peptide UP-7 potently inhibits angiogenesis and tumor growth

Abstract The recombinant kringle domain of urokinase-type plasminogen activator (UK1) has been shown to inhibit angiogenesis in vitro and in vivo and suppress brain tumor in vivo. UK1 consists of 83 amino acids and has 2 short helices, rudimentary ß-sheets and one extended antiparallel ß-sheets regions. In order to identify functional core sequence of the UK1 for angiogenesis inhibition, we examined the anti-angiogenic and anti-tumor activities for the seven UK1-derived peptides. Among the tested peptides, UP-7 potently inhibited the proliferation and migration of endothelial cells in vitro and suppressed vessel formation in Matrigel plugs in vivo. However, such anti-angiogenic activities were not exerted by the scrambled peptide UP7-SC7 or UP7-derived shorter peptides. UP-7 also suppressed VEGF-induced phosphorylation of FAK and ERK1/2 in endothelial cells. In a NCI-H460 lung cancer xenografted animal model, UP-7 effectively inhibited tumor growth. In addition, treatment of mice bearing MDA-MB231 tumor with UP-7 peptide resulted in a dose-dependent inhibition of tumor growth. Taken together, these results suggest that UK1- derived novel peptide UP-7 can be used for treatment of cancers. (NRF-2012R1A1A2007175). Citation Format: Hyun-Kyung Kim, Purevjargal Naidansuren, Seung Woo Lee, Young Ae Joe. Urokinase kringle-derived peptide UP-7 potently inhibits angiogenesis and tumor growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3799. doi:10.1158/1538-7445.AM2014-3799