Oncotarget

Research Papers:

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

Yi-Wen Chang, Chih-Ming Su, Yen-Hao Su, Yuan-Soon Ho, Hui-Huang Lai, Hsin-An Chen, Min-Liang Kuo, Jen-Liang Su, Ya-Wen Chen, Chih-Hsiung Wu, Pai-Sheng Chen and Jen-Liang Su _

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Oncotarget. 2014; 5:3823-3835. https://doi.org/10.18632/oncotarget.1709

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Abstract

Yi-Wen Chang1,2,3*, Chih-Ming Su4,5*, Yen-Hao Su3,5, Yuan-Soon Ho4,6, Hui-Huang Lai3,7, Hsin-An Chen3,4,5, Min-Liang Kuo8, Wen-Chun Hung3, Ya-Wen Chen3, Chih-Hsiung Wu4,5, Pai-Sheng Chen7,9, Jen-Liang Su3,10,11,12

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: [email protected]

Dr. Pai-Sheng Chen, e-mail: [email protected]

Dr. Chih-Hsiung Wu, e-mail: [email protected]

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.


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