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Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo

AIMS: The aim of this study was to investigate the antimetastatic effect of multiple antigenic polypeptide (MAP) vaccine based on B-cell epitopes of heparanase (HPSE) on human hepatocellular carcinoma (HCC) in vivo. METHODS: The antiserum against B-cell epitopes of HPSE was isolated, purified and ch...

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Autores principales: Zhang, Jun, Yang, Jian-min, Wang, Hui-ju, Ru, Guo-qing, Fan, Dai-ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538634/
https://www.ncbi.nlm.nih.gov/pubmed/23308126
http://dx.doi.org/10.1371/journal.pone.0052940
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author Zhang, Jun
Yang, Jian-min
Wang, Hui-ju
Ru, Guo-qing
Fan, Dai-ming
author_facet Zhang, Jun
Yang, Jian-min
Wang, Hui-ju
Ru, Guo-qing
Fan, Dai-ming
author_sort Zhang, Jun
collection PubMed
description AIMS: The aim of this study was to investigate the antimetastatic effect of multiple antigenic polypeptide (MAP) vaccine based on B-cell epitopes of heparanase (HPSE) on human hepatocellular carcinoma (HCC) in vivo. METHODS: The antiserum against B-cell epitopes of HPSE was isolated, purified and characterized after immunizing white-hair-black-eye (WHBY) rabbit with freshly synthesized MAP vaccine. Tumor-bearing murine models of orthotopic implants using HCC-97H cell line were built in BALB/c nude mice. Anti-MAP polyclonal antibodies induced by MAP vaccine were administrated to the models. The impact on metastasis was assessed, the expressions of VEGF/bFGF in hepatoma tissues and in murine sera were evaluated, and the micro-vessel density (MVD) was counted as well. In addition, the possible impairments of the HPSE MAP vaccine on certain HPSE positive normal organs and blood cells were investigated. RESULTS: The antiserum was harvested, purified and identified. The antibodies induced by MAP vaccine could specifically react with the dominant epitopes of both precursor protein and large subunit monomer of HPSE, markedly decrease HPSE activity, suppress the expressions of both VEGF and bFGF, and reduce the MVD. Pulmonary metastasis was also attenuated significantly by the anti-MAP polyclonal antibodies. In addition, no obvious impairment could be observed in certain HPSE positive organs and cells. CONCLUSION: MAP vaccine based on B-cell epitopes of HPSE is capable of alleviating HCC metastasis in vivo, mainly through inhibiting the HPSE activity and tumor associated angiogenesis, by virtue of the specific anti-MAP polyclonal antibodies. Furthermore, these HPSE-specific antibodies do not cause obvious abnormalities on certain HPSE positive blood cells and organs. Our study provides theoretical evidences for the clinical use of the synthesized MAP vaccine based on B-cell epitopes of HPSE in preventing HCC metastasis.
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spelling pubmed-35386342013-01-10 Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo Zhang, Jun Yang, Jian-min Wang, Hui-ju Ru, Guo-qing Fan, Dai-ming PLoS One Research Article AIMS: The aim of this study was to investigate the antimetastatic effect of multiple antigenic polypeptide (MAP) vaccine based on B-cell epitopes of heparanase (HPSE) on human hepatocellular carcinoma (HCC) in vivo. METHODS: The antiserum against B-cell epitopes of HPSE was isolated, purified and characterized after immunizing white-hair-black-eye (WHBY) rabbit with freshly synthesized MAP vaccine. Tumor-bearing murine models of orthotopic implants using HCC-97H cell line were built in BALB/c nude mice. Anti-MAP polyclonal antibodies induced by MAP vaccine were administrated to the models. The impact on metastasis was assessed, the expressions of VEGF/bFGF in hepatoma tissues and in murine sera were evaluated, and the micro-vessel density (MVD) was counted as well. In addition, the possible impairments of the HPSE MAP vaccine on certain HPSE positive normal organs and blood cells were investigated. RESULTS: The antiserum was harvested, purified and identified. The antibodies induced by MAP vaccine could specifically react with the dominant epitopes of both precursor protein and large subunit monomer of HPSE, markedly decrease HPSE activity, suppress the expressions of both VEGF and bFGF, and reduce the MVD. Pulmonary metastasis was also attenuated significantly by the anti-MAP polyclonal antibodies. In addition, no obvious impairment could be observed in certain HPSE positive organs and cells. CONCLUSION: MAP vaccine based on B-cell epitopes of HPSE is capable of alleviating HCC metastasis in vivo, mainly through inhibiting the HPSE activity and tumor associated angiogenesis, by virtue of the specific anti-MAP polyclonal antibodies. Furthermore, these HPSE-specific antibodies do not cause obvious abnormalities on certain HPSE positive blood cells and organs. Our study provides theoretical evidences for the clinical use of the synthesized MAP vaccine based on B-cell epitopes of HPSE in preventing HCC metastasis. Public Library of Science 2013-01-07 /pmc/articles/PMC3538634/ /pubmed/23308126 http://dx.doi.org/10.1371/journal.pone.0052940 Text en © 2013 Zhang et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Zhang, Jun
Yang, Jian-min
Wang, Hui-ju
Ru, Guo-qing
Fan, Dai-ming
Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo
title Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo
title_full Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo
title_fullStr Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo
title_full_unstemmed Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo
title_short Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo
title_sort synthesized multiple antigenic polypeptide vaccine based on b-cell epitopes of human heparanase could elicit a potent antimetastatic effect on human hepatocellular carcinoma in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538634/
https://www.ncbi.nlm.nih.gov/pubmed/23308126
http://dx.doi.org/10.1371/journal.pone.0052940
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