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Open Access Research

The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis

Charalampos Birmpas1, Jean Paul Briand2, Josẻ Courty3 and Panagiotis Katsoris1*

Author Affiliations

1 Department of Biology, University of Patras, Patras, Greece

2 CNRS, Université Paris Est Créteil, Créteil Cedex, France

3 CNRS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France

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Vascular Cell 2012, 4:21  doi:10.1186/2045-824X-4-21

Published: 24 December 2012

Abstract

Background

Nucleolin is a protein over-expressed on the surface of tumor and endothelial cells. Recent studies have underlined the involvement of cell surface nucleolin in tumor growth and angiogenesis. This cell surface molecule serves as a receptor for various ligands implicated in pathophysiological processes such as growth factors, cell adhesion molecules like integrins, selectins or laminin-1, lipoproteins and viruses (HIV and coxsackie B). HB-19 is a synthetic multimeric pseudopeptide that binds cell surface expressed nucleolin and inhibits both tumor growth and angiogenesis.

Methodology/principal findings

In the present work, we further investigated the biological actions of pseudopeptide HB-19 on HUVECs. In a previous work, we have shown that HB-19 inhibits the in vivo angiogenesis on the chicken embryo CAM assay. We now provide evidence that HB-19 inhibits the in vitro adhesion, migration and proliferation of HUVECs without inducing their apoptosis. The above biological actions seem to be regulated by SRC, ERK1/2, AKT and FAK kinases as we found that HB-19 inhibits their activation in HUVECs. Matrix metalloproteinases (MMPs) play crucial roles in tumor growth and angiogenesis, so we investigated the effect of HB-19 on the expression of MMP-2 and we found that HB-19 downregulates MMP-2 in HUVECs. Finally, down regulation of nucleolin using siRNA confirmed the implication of nucleolin in the biological actions of these peptides.

Conclusions/significance

Taken together, these results indicate that HB-19 could constitute an interesting tool for tumor therapy strategy, targeting cell surface nucleolin.