Journal
ONCOTARGET
Volume 5, Issue 11, Pages 3823-3835Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.1709
Keywords
VEGFR-3; VEGFR-3-targeting peptides; metastasis; drug resistance
Categories
Funding
- National Science Council from Taiwan [NSC 102-2314-B-039-200, NSC 102-2314-B-038-028-MY3, NSC 101-2320-B-400-016-MY3, NSC 101-2320-B-006-045-MY2]
- National Health Research Institutes from Taiwan [CA-102-PP-41]
- Ministry of Health and Welfare, Taiwan [DOH101-TD-PB-111-NSC015, DOH 102-TD-C-111-004]
- Ministry of Education, Taiwan [D102-22005, D103-35004, D103-35005]
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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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