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The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis
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 pathophysiolog...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606460/ https://www.ncbi.nlm.nih.gov/pubmed/23265284 http://dx.doi.org/10.1186/2045-824X-4-21 |
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author | Birmpas, Charalampos Briand, Jean Paul Courty, Josẻ Katsoris, Panagiotis |
author_facet | Birmpas, Charalampos Briand, Jean Paul Courty, Josẻ Katsoris, Panagiotis |
author_sort | Birmpas, Charalampos |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3606460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36064602013-03-24 The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis Birmpas, Charalampos Briand, Jean Paul Courty, Josẻ Katsoris, Panagiotis Vasc Cell Research 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. BioMed Central 2012-12-24 /pmc/articles/PMC3606460/ /pubmed/23265284 http://dx.doi.org/10.1186/2045-824X-4-21 Text en Copyright ©2012 Birmpas et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Birmpas, Charalampos Briand, Jean Paul Courty, Josẻ Katsoris, Panagiotis The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis |
title | The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis |
title_full | The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis |
title_fullStr | The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis |
title_full_unstemmed | The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis |
title_short | The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis |
title_sort | pseudopeptide hb-19 binds to cell surface nucleolin and inhibits angiogenesis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606460/ https://www.ncbi.nlm.nih.gov/pubmed/23265284 http://dx.doi.org/10.1186/2045-824X-4-21 |
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