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Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models
To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovasc...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496375/ https://www.ncbi.nlm.nih.gov/pubmed/25868854 |
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author | Cicatiello, Valeria Apicella, Ivana Tudisco, Laura Tarallo, Valeria Formisano, Luigi Sandomenico, Annamaria Kim, Younghee Bastos-Carvalho, Ana Orlandi, Augusto Ambati, Jayakrishna Ruvo, Menotti Bianco, Roberto De Falco, Sandro |
author_facet | Cicatiello, Valeria Apicella, Ivana Tudisco, Laura Tarallo, Valeria Formisano, Luigi Sandomenico, Annamaria Kim, Younghee Bastos-Carvalho, Ana Orlandi, Augusto Ambati, Jayakrishna Ruvo, Menotti Bianco, Roberto De Falco, Sandro |
author_sort | Cicatiello, Valeria |
collection | PubMed |
description | To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit macrophages migration. iVR1 was able to synergize with irinotecan determining a shrinkage of tumors that became undetectable after three weeks of combined treatment. Such treatment induced a significant prolongation of survival similar to that observed with bevacizumab and irinotecan combination. iVR1 also fully prevented lung invasion by HCT-116 cells injected in mouse tail vein. Also, iVR1 impressively inhibited choroid neovascularization after a single intravitreal injection. Collectively, data showed the strong potential of iVR1 peptide as a new anti-tumor and anti-metastatic agent and demonstrate the high flexibility of VEGFR1 antagonists as therapeutic anti-angiogenic agents in different pathological contexts. |
format | Online Article Text |
id | pubmed-4496375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-44963752015-07-15 Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models Cicatiello, Valeria Apicella, Ivana Tudisco, Laura Tarallo, Valeria Formisano, Luigi Sandomenico, Annamaria Kim, Younghee Bastos-Carvalho, Ana Orlandi, Augusto Ambati, Jayakrishna Ruvo, Menotti Bianco, Roberto De Falco, Sandro Oncotarget Research Paper To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit macrophages migration. iVR1 was able to synergize with irinotecan determining a shrinkage of tumors that became undetectable after three weeks of combined treatment. Such treatment induced a significant prolongation of survival similar to that observed with bevacizumab and irinotecan combination. iVR1 also fully prevented lung invasion by HCT-116 cells injected in mouse tail vein. Also, iVR1 impressively inhibited choroid neovascularization after a single intravitreal injection. Collectively, data showed the strong potential of iVR1 peptide as a new anti-tumor and anti-metastatic agent and demonstrate the high flexibility of VEGFR1 antagonists as therapeutic anti-angiogenic agents in different pathological contexts. Impact Journals LLC 2015-03-25 /pmc/articles/PMC4496375/ /pubmed/25868854 Text en Copyright: © 2015 Cicatiello et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Cicatiello, Valeria Apicella, Ivana Tudisco, Laura Tarallo, Valeria Formisano, Luigi Sandomenico, Annamaria Kim, Younghee Bastos-Carvalho, Ana Orlandi, Augusto Ambati, Jayakrishna Ruvo, Menotti Bianco, Roberto De Falco, Sandro Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models |
title | Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models |
title_full | Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models |
title_fullStr | Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models |
title_full_unstemmed | Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models |
title_short | Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models |
title_sort | powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496375/ https://www.ncbi.nlm.nih.gov/pubmed/25868854 |
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