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The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α(v)β(3) integrin in chick embryo and nude mouse models

Echistatin, a cyclic RGD peptide, which is an antagonist of α(v)β(3) integrin (disintegrin), inhibited human osteosarcoma in the chick chorioallontoic membrane (CAM) model and tumor growth and pulmonary metastases in a nude mouse orthotopic model. A high-metastatic variant of human osteosarcoma, 143...

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Autores principales: Tome, Yasunori, Kimura, Hiroaki, Sugimoto, Naotoshi, Tsuchiya, Hiroyuki, Kanaya, Fuminori, Bouvet, Michael, Hoffman, Robert M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349968/
https://www.ncbi.nlm.nih.gov/pubmed/27894082
http://dx.doi.org/10.18632/oncotarget.13497
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author Tome, Yasunori
Kimura, Hiroaki
Sugimoto, Naotoshi
Tsuchiya, Hiroyuki
Kanaya, Fuminori
Bouvet, Michael
Hoffman, Robert M.
author_facet Tome, Yasunori
Kimura, Hiroaki
Sugimoto, Naotoshi
Tsuchiya, Hiroyuki
Kanaya, Fuminori
Bouvet, Michael
Hoffman, Robert M.
author_sort Tome, Yasunori
collection PubMed
description Echistatin, a cyclic RGD peptide, which is an antagonist of α(v)β(3) integrin (disintegrin), inhibited human osteosarcoma in the chick chorioallontoic membrane (CAM) model and tumor growth and pulmonary metastases in a nude mouse orthotopic model. A high-metastatic variant of human osteosarcoma, 143B-LM4, overexpressing α(v)β(3) integrin was used. Tumor angiogenesis by high-metastatic variant 143B-LM4 cells in the CAM was significantly inhibited by echistatin (P<0.05) as was overall growth. A doxorubicin (DOX)-echistatin combination inhibited orthotopic tumor growth compared to untreated control (P<0.01) or DOX alone (P<0.05) in nude mice. Tumor-bearing mice treated with the DOX-echistatin combination survived longer than those treated with DOX alone or control PBS (P<0.01 and P<0.01, respectively). Echistatin also inhibited experimental lung metastasis of 143B-LM4 cells in nude mice. These results suggest that DOX in combination with a disintegrin has potential to treat osteosarcoma and that α(v)β(3) integrin may be a target for osteosarcoma.
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spelling pubmed-53499682017-04-06 The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α(v)β(3) integrin in chick embryo and nude mouse models Tome, Yasunori Kimura, Hiroaki Sugimoto, Naotoshi Tsuchiya, Hiroyuki Kanaya, Fuminori Bouvet, Michael Hoffman, Robert M. Oncotarget Research Paper Echistatin, a cyclic RGD peptide, which is an antagonist of α(v)β(3) integrin (disintegrin), inhibited human osteosarcoma in the chick chorioallontoic membrane (CAM) model and tumor growth and pulmonary metastases in a nude mouse orthotopic model. A high-metastatic variant of human osteosarcoma, 143B-LM4, overexpressing α(v)β(3) integrin was used. Tumor angiogenesis by high-metastatic variant 143B-LM4 cells in the CAM was significantly inhibited by echistatin (P<0.05) as was overall growth. A doxorubicin (DOX)-echistatin combination inhibited orthotopic tumor growth compared to untreated control (P<0.01) or DOX alone (P<0.05) in nude mice. Tumor-bearing mice treated with the DOX-echistatin combination survived longer than those treated with DOX alone or control PBS (P<0.01 and P<0.01, respectively). Echistatin also inhibited experimental lung metastasis of 143B-LM4 cells in nude mice. These results suggest that DOX in combination with a disintegrin has potential to treat osteosarcoma and that α(v)β(3) integrin may be a target for osteosarcoma. Impact Journals LLC 2016-11-22 /pmc/articles/PMC5349968/ /pubmed/27894082 http://dx.doi.org/10.18632/oncotarget.13497 Text en Copyright: © 2016 Tome et al. http://creativecommons.org/licenses/by/3.0/ 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
Tome, Yasunori
Kimura, Hiroaki
Sugimoto, Naotoshi
Tsuchiya, Hiroyuki
Kanaya, Fuminori
Bouvet, Michael
Hoffman, Robert M.
The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α(v)β(3) integrin in chick embryo and nude mouse models
title The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α(v)β(3) integrin in chick embryo and nude mouse models
title_full The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α(v)β(3) integrin in chick embryo and nude mouse models
title_fullStr The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α(v)β(3) integrin in chick embryo and nude mouse models
title_full_unstemmed The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α(v)β(3) integrin in chick embryo and nude mouse models
title_short The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α(v)β(3) integrin in chick embryo and nude mouse models
title_sort disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α(v)β(3) integrin in chick embryo and nude mouse models
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349968/
https://www.ncbi.nlm.nih.gov/pubmed/27894082
http://dx.doi.org/10.18632/oncotarget.13497
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