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Angiogenesis. 2018 Aug;21(3):653-665. doi: 10.1007/s10456-018-9616-7. Epub 2018 Apr 24.

Angio-3, a 10-residue peptide derived from human plasminogen kringle 3, suppresses tumor growth in mice via impeding both angiogenesis and vascular permeability.

Author information

1
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore.
2
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore. dbsgerw@nus.edu.sg.

Abstract

Anti-angiogenesis therapy is an established therapeutic strategy for cancer. The endogenous angiogenic inhibitor angiostatin contains the first 3-4 kringle domains of plasminogen and inhibits both angiogenesis and vascular permeability. We present here a 10-residue peptide, Angio-3, derived from plasminogen kringle 3, which retains the functions of angiostatin in inhibiting both angiogenesis and vascular permeability. NMR studies indicate that Angio-3 holds a solution structure similar to the corresponding region of kringle 3. Mechanistically, Angio-3 inhibited both VEGF- and bFGF-induced angiogenesis by inhibiting EC proliferation and migration while inducing apoptosis. Inhibition of VEGF-induced vascular permeability results from its ability to impede VEGF-induced dissociation of adherens junction and tight junction proteins as well as the formation of actin stress fibers. When administered intravenously, Angio-3 inhibited subcutaneous breast cancer and melanoma growth by suppressing both tumor angiogenesis and intra-tumor vascular permeability. Hence, Angio-3 is a novel dual inhibitor of angiogenesis and vascular permeability. It is valuable as a lead peptide that can be further developed as therapeutics for diseases involving excessive angiogenesis and/or vascular permeability.

KEYWORDS:

Angiogenesis; Kringle domain; Peptide; Plasminogen; Vascular permeability

PMID:
29691683
DOI:
10.1007/s10456-018-9616-7

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