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Alphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical model

Most characterized angiogenic modulators are proteolytic fragments of structural plasma and/or matrix components. Herein, we have identified a novel anti-angiogenic peptide generated by the in vitro hydrolysis of the C-terminal moiety of the fibrinogen alpha chain, produced by the snake venom metall...

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Autores principales: Ferreira, Adilson Kleber, Cristofaro, Brunella, Menezes, Milene Cristina, de Oliveira, Ana Karina, Tashima, Alexandre Keiji, de Melo, Robson Lopes, Silva, Cristiane Castilho Fernandes, Rodriguez, Miryam Guillermina Palomino, Carvalho, Daniela Cajado de Oliveira Souza, de Azevedo, Ricardo Alexandre, Junior, Paulo Luiz de Sá, Mambelli, Lisley Inata, Portaro, Fernanda Vieira, Pardanaud, Luc, Eichmann, Anne, Sant’Anna, Osvaldo Augusto, Faria, Mxarcella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771711/
https://www.ncbi.nlm.nih.gov/pubmed/33473260
http://dx.doi.org/10.18632/oncotarget.27839
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author Ferreira, Adilson Kleber
Cristofaro, Brunella
Menezes, Milene Cristina
de Oliveira, Ana Karina
Tashima, Alexandre Keiji
de Melo, Robson Lopes
Silva, Cristiane Castilho Fernandes
Rodriguez, Miryam Guillermina Palomino
Carvalho, Daniela Cajado de Oliveira Souza
de Azevedo, Ricardo Alexandre
Junior, Paulo Luiz de Sá
Mambelli, Lisley Inata
Portaro, Fernanda Vieira
Pardanaud, Luc
Eichmann, Anne
Sant’Anna, Osvaldo Augusto
Faria, Mxarcella
author_facet Ferreira, Adilson Kleber
Cristofaro, Brunella
Menezes, Milene Cristina
de Oliveira, Ana Karina
Tashima, Alexandre Keiji
de Melo, Robson Lopes
Silva, Cristiane Castilho Fernandes
Rodriguez, Miryam Guillermina Palomino
Carvalho, Daniela Cajado de Oliveira Souza
de Azevedo, Ricardo Alexandre
Junior, Paulo Luiz de Sá
Mambelli, Lisley Inata
Portaro, Fernanda Vieira
Pardanaud, Luc
Eichmann, Anne
Sant’Anna, Osvaldo Augusto
Faria, Mxarcella
author_sort Ferreira, Adilson Kleber
collection PubMed
description Most characterized angiogenic modulators are proteolytic fragments of structural plasma and/or matrix components. Herein, we have identified a novel anti-angiogenic peptide generated by the in vitro hydrolysis of the C-terminal moiety of the fibrinogen alpha chain, produced by the snake venom metalloprotease bothropasin (SVMP), a hemorrhagic proteinase in Bothrops jararaca venom. The 14-amino acids peptide (alphastatin-C) is a potent antagonist of basic fibroblast growth factor, induced endothelial cell (HUVEC-CS) proliferation, migration and capillary tube formation in matrigel. It also inhibits cell adhesion to fibronectin. The basis of the antagonism between bFGF and alphastatin-C is elucidated by the inhibition of various bFGF induced signaling pathways and their molecular components modification, whenever the combination of the stimuli is provided, in comparison to the treatment with bFGF only. To corroborate to the potential therapeutic use of alphastatin-C, we have chosen to perform in vivo assays in two distinct angiogenic settings. In chick model, alphastatin-C inhibits chorioallantoic membrane angiogenesis. In mouse, it efficiently reduces tumor number and volume in a melanoma model, due to the impairment of tumor neovascularization in treated mice. In contrast, we show that the alphastatin-C peptide induces arteriogenesis, increasing pial collateral density in neonate mice. alphastatin-C is an efficient new antiangiogenic FGF-associated agent in vitro, it is an inhibitor of embryonic and tumor vascularization in vivo while, it is an arteriogenic agent. The results also suggest that SVMPs can be used as in vitro biochemical tools to process plasma and/or matrix macromolecular components unraveling new angiostatic peptides.
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spelling pubmed-77717112021-01-19 Alphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical model Ferreira, Adilson Kleber Cristofaro, Brunella Menezes, Milene Cristina de Oliveira, Ana Karina Tashima, Alexandre Keiji de Melo, Robson Lopes Silva, Cristiane Castilho Fernandes Rodriguez, Miryam Guillermina Palomino Carvalho, Daniela Cajado de Oliveira Souza de Azevedo, Ricardo Alexandre Junior, Paulo Luiz de Sá Mambelli, Lisley Inata Portaro, Fernanda Vieira Pardanaud, Luc Eichmann, Anne Sant’Anna, Osvaldo Augusto Faria, Mxarcella Oncotarget Research Paper Most characterized angiogenic modulators are proteolytic fragments of structural plasma and/or matrix components. Herein, we have identified a novel anti-angiogenic peptide generated by the in vitro hydrolysis of the C-terminal moiety of the fibrinogen alpha chain, produced by the snake venom metalloprotease bothropasin (SVMP), a hemorrhagic proteinase in Bothrops jararaca venom. The 14-amino acids peptide (alphastatin-C) is a potent antagonist of basic fibroblast growth factor, induced endothelial cell (HUVEC-CS) proliferation, migration and capillary tube formation in matrigel. It also inhibits cell adhesion to fibronectin. The basis of the antagonism between bFGF and alphastatin-C is elucidated by the inhibition of various bFGF induced signaling pathways and their molecular components modification, whenever the combination of the stimuli is provided, in comparison to the treatment with bFGF only. To corroborate to the potential therapeutic use of alphastatin-C, we have chosen to perform in vivo assays in two distinct angiogenic settings. In chick model, alphastatin-C inhibits chorioallantoic membrane angiogenesis. In mouse, it efficiently reduces tumor number and volume in a melanoma model, due to the impairment of tumor neovascularization in treated mice. In contrast, we show that the alphastatin-C peptide induces arteriogenesis, increasing pial collateral density in neonate mice. alphastatin-C is an efficient new antiangiogenic FGF-associated agent in vitro, it is an inhibitor of embryonic and tumor vascularization in vivo while, it is an arteriogenic agent. The results also suggest that SVMPs can be used as in vitro biochemical tools to process plasma and/or matrix macromolecular components unraveling new angiostatic peptides. Impact Journals LLC 2020-12-22 /pmc/articles/PMC7771711/ /pubmed/33473260 http://dx.doi.org/10.18632/oncotarget.27839 Text en Copyright: © 2020 Ferreira et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ferreira, Adilson Kleber
Cristofaro, Brunella
Menezes, Milene Cristina
de Oliveira, Ana Karina
Tashima, Alexandre Keiji
de Melo, Robson Lopes
Silva, Cristiane Castilho Fernandes
Rodriguez, Miryam Guillermina Palomino
Carvalho, Daniela Cajado de Oliveira Souza
de Azevedo, Ricardo Alexandre
Junior, Paulo Luiz de Sá
Mambelli, Lisley Inata
Portaro, Fernanda Vieira
Pardanaud, Luc
Eichmann, Anne
Sant’Anna, Osvaldo Augusto
Faria, Mxarcella
Alphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical model
title Alphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical model
title_full Alphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical model
title_fullStr Alphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical model
title_full_unstemmed Alphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical model
title_short Alphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical model
title_sort alphastatin-c a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards b16-f10 melanoma growth in a preclinical model
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771711/
https://www.ncbi.nlm.nih.gov/pubmed/33473260
http://dx.doi.org/10.18632/oncotarget.27839
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