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Open Access Research article

Nucleolin mediates the antiangiogenesis effect of the pseudopeptide N6L

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

Author Affiliations

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

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

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

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BMC Cell Biology 2012, 13:32  doi:10.1186/1471-2121-13-32

Published: 13 November 2012

Abstract

Background

Nucleolin is a protein over-expressed on the surface of activated cells. Recent studies have underlined the involvement of cell surface nucleolin in angiogenesis processes. 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. N6L is a synthetic multimeric pseudopeptide that binds cell surface expressed nucleolin and inhibits cell proliferation.

Results

In the present work, we further investigated the mechanisms of action of pseudopeptide N6L on angiogenesis using HUVECs. We provide evidence that N6L inhibits the in vitro adhesion, proliferation and migration of HUVECs without inducing their apoptosis. In addition, we found that N6L downregulates MMP-2 in HUVECs. The above biological actions are regulated by SRC, ERK1/2, AKT and FAK kinases as we found that N6L inhibits their activation in HUVECs. Finally, down regulation of nucleolin using siRNA demonstrated the implication of nucleolin in the biological actions of these peptides.

Conclusions

Taken together, these results indicate that N6L could constitute an interesting therapeutic tool for treating diseases associated with excessive angiogenesis.

Keywords:
Angiogenesis; Nucleolin; Cancer; N6L; HB-19