Novel peptides suppress VEGFR-3 activity and antagonize VEGFR-3-mediated oncogenic effects

Abstract

$('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); Yi-Wen Chang 1 , 2 , 3 * , Chih-Ming Su 4 , 5 * , Yen-Hao Su 3 , 5 , Yuan-Soon Ho 4 , 6 , Hui-Huang Lai 3 , 7 , Hsin-An Chen 3 , 4 , 5 , Min-Liang Kuo 8 , Wen-Chun Hung 3 , Ya-Wen Chen 3 , Chih-Hsiung Wu 4 , 5 , Pai-Sheng Chen 7 , 9 , Jen-Liang Su 3 , 10 , 11 , 12 1 Graduate Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan 2 Genomics Research Center, Academia Sinica, Taipei 115, Taiwan 3 National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan 4 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan 5 Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University 6 School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University 7 Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan 8 College of life Science, National Taiwan University, Taipei 106, Taiwan 9 Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan 10 Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung 404, Taiwan 11 Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan 12 Department of Biotechnology, Asia University, Taichung 404, Taiwan * These authors contribute equally in this study. Correspondence to: Dr. Jen-Liang Su, e-mail: jlsu@nhri.org.tw Dr. Pai-Sheng Chen, e-mail: bio.benson@gmail.com Dr. Chih-Hsiung Wu, e-mail: chwu@tmu.edu.tw Key words: VEGFR-3, VEGFR-3-targeting peptides, metastasis, drug resistance Received: December 20, 2013      Accepted: May 18, 2014      Published: May 20, 2014 ABSTRACT Vascular endothelial growth factor receptor 3 (VEGFR-3) supports tumor lymphangiogenesis. It was originally identified as a lymphangiogenic factor expressed in lymphatic endothelial cells. VEGFR-3 was detected in advanced human malignancies and correlated with poor prognosis. Our previous studies show that activation of the VEGF-C/VEGFR-3 axis promotes cancer metastasis and is associated with clinical progression in patients with lung cancer, indicating that VEGFR-3 is a potential target for cancer therapy. In this study, we developed eight peptides targeting VEGFR-3. Two peptides strongly inhibited the kinase activity of VEGFR-3 and suppressed VEGF-C-mediated invasion of cancer cells. Moreover, these peptides abolished VEGF-C-induced drug resistance and tumor initiating cell formation. This study demonstrates the therapeutic potential of VEGFR-3-targeting peptides.