title: Novel peptides suppress VEGFR-3 activity and antagonize VEGFR-3-mediated oncogenic effects.
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.
authors.affiliation: Graduate Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chang
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Su
authors.forename: Yen-Hao
authors.initials: YH
authors.lastname: Su
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
authors.forename: Hui-Huang
authors.initials: HH
authors.lastname: Lai
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Chen
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Hung
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University.
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan; Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Pai-Sheng
authors.initials: PS
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan; Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung 404, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 404, Taiwan.
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D010455:Peptides; C581309:FLT4 protein, human; D040321:Vascular Endothelial Growth Factor Receptor-3