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: 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
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 11 Pg. 3823-35 (Jun 15 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 25003617 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• FLT4 protein, human
• Vascular Endothelial Growth Factor Receptor-3

Topics

• Adenocarcinoma (drug therapy, genetics, metabolism)
• Adenocarcinoma of Lung
• Animals
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Disease Progression
• Drug Resistance, Neoplasm
• Female
• HEK293 Cells
• Heterografts
• Humans
• Lung Neoplasms (drug therapy, genetics, metabolism)
• MCF-7 Cells
• Mice
• Mice, SCID
• Neoplasm Metastasis
• Peptides (pharmacology)
• Phosphorylation
• Vascular Endothelial Growth Factor Receptor-3 (antagonists & inhibitors, genetics, metabolism)