Inhibition of tumour angiogenesis using synthetic peptides

Article information
Efficient inhibition of tumor angiogenesis and growth by a synthetic peptide blocking S100A4-methionine aminopeptidase 2 interaction.
Ochiya T, Takenaga K, Asagiri M, Nakano K, Satoh H, Watanabe T, Imajoh-Ohmi S, Endo H.
Mol Ther Methods Clin Dev. 2015 Apr 1;2:15008. PMID: 26029719

Overview
A calcium-binding protein, S100A4, has been reported as a protein that promotes cancer invasion and metastasis.

In previous work, the authors reported that MetAP2, which controls phosphorylation of eIF2α and ERK1 / 2, is an effector protein of S100A4, with the S100A4 binding site (SBD) residing within the region of MetAP2 lying between amino acid residues 170 and 229.

In the study described here, three synthetic peptides [(1) the entire SBD peptide, (2) the N-terminal segment of the SBD (aa 170-208, designated NBD), and (3) the C-terminal segment of the SBD (aa 192-229 residues, designated CBD)] were synthesized, and the effects of each peptide were evaluated in terms of (a) the inhibition of binding of S100A4 and MetAP2 and (b) the inhibition of angiogenesis.

When the authors administered peptides to mouse vascular endothelial cells, the formation of capillary vessels was significantly suppressed in the NBD peptide administration group. Similarly, when peptides were added to an angioreactor containing the angiogenesis promoting factor, significant suppression of angiogenesis was observed only in the NBD peptide group.

Furthermore, the administration of the NBD peptide to the mouse xenograft tumour model resulted in inhibition of angiogenesis and tumour growth.

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