Nucleolin mediates the antiangiogenesis effect of the pseudopeptide N6L

BMC Cell Biology

Panagiotis Katsoris¹  Josẻ Courty³  Jean Paul Briand²  Charalampos Birmpas¹ 

[1] Department of Biology, University of Patras, Patras, Greece;Université Paris Est Créteil, CNRS, Créteil Cedex, France;CNRS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France

关键词: HB-19;    N6L;    Cancer;    Nucleolin;    Angiogenesis;   

Others  :  856683
DOI  :  10.1186/1471-2121-13-32

 received in 2012-07-31, accepted in 2012-11-04,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Birmpas et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 5.

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