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CSP I-plus modified rEndostatin inhibits hepatocellular carcinoma metastasis via down-regulation of VEGFA and integrinβ1

BACKGROUND: In our previous study, N end of the Circumsporozoite protein (CSP I-plus) modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed, which had antiangiogenic capability and bound to hepatocellular carcinoma in vivo and in vitro. In this study, the inhibition...

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Autores principales: Chen, Xueqin, Wang, Yan, Liu, Hancong, Zhang, Jingjing, Wang, Jie, Jin, Xiaobao, Ma, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682839/
https://www.ncbi.nlm.nih.gov/pubmed/36419008
http://dx.doi.org/10.1186/s12885-022-10318-8
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author Chen, Xueqin
Wang, Yan
Liu, Hancong
Zhang, Jingjing
Wang, Jie
Jin, Xiaobao
Ma, Yan
author_facet Chen, Xueqin
Wang, Yan
Liu, Hancong
Zhang, Jingjing
Wang, Jie
Jin, Xiaobao
Ma, Yan
author_sort Chen, Xueqin
collection PubMed
description BACKGROUND: In our previous study, N end of the Circumsporozoite protein (CSP I-plus) modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed, which had antiangiogenic capability and bound to hepatocellular carcinoma in vivo and in vitro. In this study, the inhibition of rES-CSP on hepatocellular carcinoma metastasis was verified in vivo and in vitro, and its possible mechanism was explored. METHODS: Firstly, the impact of rES-CSP on the migration, adhesion of hepatoma cell HCCLM3 was identified by wound healing, transwell, and on metastasis of orthotopic xenograft model was identified in nude mouse. Then the expression of metastasis-associated molecules (MMP2, E-cadherin, integrinβ1) and angiogenesis-related factors (VEGFA) in vitro and in vivo were detected by real-time PCR, western blotting, immunohistochemistry. RESULTS: Finally, we found that rES-CSP could inhibit the migration and invasion of HCCLM3, and decrease tumor metastasis and growth in nude mouse orthotopic xenograft models. The tumor inhibiting rates of rES-CSP and Endostar were 42.46 ± 5.39% and 11.1 ± 1.88%. The lung metastasis rates of the control, Endostar and rES-CSP were 71, 50, and 42.8%, respectively. Compared with Endostar, rES-CSP significantly down-regulated the expression of VEGFA and integrinβ1. Heparin, a competitive inhibitor of CSP I-plus, which can be bind to the highly-sulfated heparan sulfate proteoglycans (HSPGs) over-expressed in liver and hepatocellular carcinoma, alleviated the down-regulation of VEGFA and integrinβ1. CONCLUSIONS: These indicate that rES-CSP may play a role in inhibiting tumor growth and metastasis by down-regulating the angiogenic factor VEGF and the metastasis-related molecules or by interfering with HSPGs-mediated tumor metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10318-8.
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spelling pubmed-96828392022-11-24 CSP I-plus modified rEndostatin inhibits hepatocellular carcinoma metastasis via down-regulation of VEGFA and integrinβ1 Chen, Xueqin Wang, Yan Liu, Hancong Zhang, Jingjing Wang, Jie Jin, Xiaobao Ma, Yan BMC Cancer Research BACKGROUND: In our previous study, N end of the Circumsporozoite protein (CSP I-plus) modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed, which had antiangiogenic capability and bound to hepatocellular carcinoma in vivo and in vitro. In this study, the inhibition of rES-CSP on hepatocellular carcinoma metastasis was verified in vivo and in vitro, and its possible mechanism was explored. METHODS: Firstly, the impact of rES-CSP on the migration, adhesion of hepatoma cell HCCLM3 was identified by wound healing, transwell, and on metastasis of orthotopic xenograft model was identified in nude mouse. Then the expression of metastasis-associated molecules (MMP2, E-cadherin, integrinβ1) and angiogenesis-related factors (VEGFA) in vitro and in vivo were detected by real-time PCR, western blotting, immunohistochemistry. RESULTS: Finally, we found that rES-CSP could inhibit the migration and invasion of HCCLM3, and decrease tumor metastasis and growth in nude mouse orthotopic xenograft models. The tumor inhibiting rates of rES-CSP and Endostar were 42.46 ± 5.39% and 11.1 ± 1.88%. The lung metastasis rates of the control, Endostar and rES-CSP were 71, 50, and 42.8%, respectively. Compared with Endostar, rES-CSP significantly down-regulated the expression of VEGFA and integrinβ1. Heparin, a competitive inhibitor of CSP I-plus, which can be bind to the highly-sulfated heparan sulfate proteoglycans (HSPGs) over-expressed in liver and hepatocellular carcinoma, alleviated the down-regulation of VEGFA and integrinβ1. CONCLUSIONS: These indicate that rES-CSP may play a role in inhibiting tumor growth and metastasis by down-regulating the angiogenic factor VEGF and the metastasis-related molecules or by interfering with HSPGs-mediated tumor metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10318-8. BioMed Central 2022-11-22 /pmc/articles/PMC9682839/ /pubmed/36419008 http://dx.doi.org/10.1186/s12885-022-10318-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chen, Xueqin
Wang, Yan
Liu, Hancong
Zhang, Jingjing
Wang, Jie
Jin, Xiaobao
Ma, Yan
CSP I-plus modified rEndostatin inhibits hepatocellular carcinoma metastasis via down-regulation of VEGFA and integrinβ1
title CSP I-plus modified rEndostatin inhibits hepatocellular carcinoma metastasis via down-regulation of VEGFA and integrinβ1
title_full CSP I-plus modified rEndostatin inhibits hepatocellular carcinoma metastasis via down-regulation of VEGFA and integrinβ1
title_fullStr CSP I-plus modified rEndostatin inhibits hepatocellular carcinoma metastasis via down-regulation of VEGFA and integrinβ1
title_full_unstemmed CSP I-plus modified rEndostatin inhibits hepatocellular carcinoma metastasis via down-regulation of VEGFA and integrinβ1
title_short CSP I-plus modified rEndostatin inhibits hepatocellular carcinoma metastasis via down-regulation of VEGFA and integrinβ1
title_sort csp i-plus modified rendostatin inhibits hepatocellular carcinoma metastasis via down-regulation of vegfa and integrinβ1
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682839/
https://www.ncbi.nlm.nih.gov/pubmed/36419008
http://dx.doi.org/10.1186/s12885-022-10318-8
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