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, Wen Chun Hung, Ya Wen Chen, Chih Hsiung Wu, Pai Sheng Chen, Jen Liang Su

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16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3823-3835
Number of pages13
JournalOncotarget
Volume5
Issue number11
Publication statusPublished - 2014

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Keywords

  • Drug resistance
  • Metastasis
  • VEGFR-3
  • VEGFR-3-targeting peptides

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this

Chang, Y. W., Su, C. M., Su, Y-H., Ho, Y. S., Lai, H. H., Chen, H. A., Kuo, M. L., Hung, W. C., Chen, Y. W., Wu, C. H., Chen, P. S., & Su, J. L. (2014). Novel peptides suppress VEGFR-3 activity and antagonize VEGFR-3-mediated oncogenic effects. Oncotarget, 5(11), 3823-3835.