Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis

Suk Hyun Choi,1,* Jue Yeon Lee,2,* Jin Sook Suh,1 Yoon Shin Park,3 Chong Pyoung Chung,2 Yoon Jeong Park1 1Department of Dental Regenerative Biotechnology, Dental Research Institute, 2Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), School of Dentistry, Seoul...

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Autores principales:	Choi SH, Lee JY, Suh JS, Park YS, Chung CP, Park YJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3cb8f1019d67474fa94e8197c5685fb7
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spelling	oai:doaj.org-article:3cb8f1019d67474fa94e8197c5685fb72021-12-02T02:10:35ZDual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis1178-2013https://doaj.org/article/3cb8f1019d67474fa94e8197c5685fb72016-09-01T00:00:00Zhttps://www.dovepress.com/dual-function-synthetic-peptide-derived-from-bmp4-for-highly-efficient-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Suk Hyun Choi,1,* Jue Yeon Lee,2,* Jin Sook Suh,1 Yoon Shin Park,3 Chong Pyoung Chung,2 Yoon Jeong Park1 1Department of Dental Regenerative Biotechnology, Dental Research Institute, 2Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), School of Dentistry, Seoul National University, Seoul, 3Department in Microbiology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, South Korea *These authors contributed equally to this work Abstract: Angiogenesis plays a critical role in the growth and metastasis of cancer, and growth factors released from cancer promote blood-vessel formation in the tumor microenvironment. The angiogenesis is accelerated via interactions of growth factors with the high-affinity receptors on cancer cells. In particular, heparan sulfate proteoglycans (HSPGs) on the surface of cancer cells have been shown to be important in many aspects of determining a tumor’s phenotype and development. Specifically, the regulation of the interactions between HSPGs and growth factors results in changes in tumor progression. A peptide with heparin-binding (HBP) activity has been developed and synthesized to inhibit tumor growth via the prevention of angiogenesis. We hypothesized that HBP could inhibit the interaction of growth factors and HSPGs on the surface of cancer cells, decrease paracrine signaling in endothelial cells (ECs), and finally decrease angiogenesis in the tumor microenvironment. In this study, we found that HBP had antiangiogenic effects in vitro and in vivo. The conditioned media obtained from a breast cancer cell line treated with HBP were used to culture human umbilical vein ECs (HUVECs) to evaluate the antiangiogenic effect of HBP on ECs. HBP effectively inhibited the migration, invasion, and tube formation of HUVECs in vitro. In addition, the expressions of angiogenesis-mediating factors, including ERK, FAK, and Akt, were considerably decreased. HBP also decreased the levels of invasive factors, including MMP2 and MMP9, secreted by the HUVECs. We demonstrated significant suppression of tumor growth in a breast cancer xenograft model and enhanced distribution of HBP at the site of tumors. Taken together, our results show that HBP has antiangiogenic effects on ECs, and suggest that it may serve as a potential antitumor agent through control of the tumor microenvironment. Keywords: heparin-binding peptide, HBP, antiangiogenesis, heparan sulfate proteoglycans, HSPGs, endothelial cells, breast cancer xenograft, tumor microenvironmentChoi SHLee JYSuh JSPark YSChung CPPark YJDove Medical PressarticleHeparin binding peptide (HBP)anti-angiogenesisheparan sulfate proteoglycans (HSPGs)endothelial cellsbreast cancer xenografttumor microenvironmentMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4643-4656 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment Medicine (General) R5-920
spellingShingle	Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment Medicine (General) R5-920 Choi SH Lee JY Suh JS Park YS Chung CP Park YJ Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
description	Suk Hyun Choi,1,* Jue Yeon Lee,2,* Jin Sook Suh,1 Yoon Shin Park,3 Chong Pyoung Chung,2 Yoon Jeong Park1 1Department of Dental Regenerative Biotechnology, Dental Research Institute, 2Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), School of Dentistry, Seoul National University, Seoul, 3Department in Microbiology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, South Korea *These authors contributed equally to this work Abstract: Angiogenesis plays a critical role in the growth and metastasis of cancer, and growth factors released from cancer promote blood-vessel formation in the tumor microenvironment. The angiogenesis is accelerated via interactions of growth factors with the high-affinity receptors on cancer cells. In particular, heparan sulfate proteoglycans (HSPGs) on the surface of cancer cells have been shown to be important in many aspects of determining a tumor’s phenotype and development. Specifically, the regulation of the interactions between HSPGs and growth factors results in changes in tumor progression. A peptide with heparin-binding (HBP) activity has been developed and synthesized to inhibit tumor growth via the prevention of angiogenesis. We hypothesized that HBP could inhibit the interaction of growth factors and HSPGs on the surface of cancer cells, decrease paracrine signaling in endothelial cells (ECs), and finally decrease angiogenesis in the tumor microenvironment. In this study, we found that HBP had antiangiogenic effects in vitro and in vivo. The conditioned media obtained from a breast cancer cell line treated with HBP were used to culture human umbilical vein ECs (HUVECs) to evaluate the antiangiogenic effect of HBP on ECs. HBP effectively inhibited the migration, invasion, and tube formation of HUVECs in vitro. In addition, the expressions of angiogenesis-mediating factors, including ERK, FAK, and Akt, were considerably decreased. HBP also decreased the levels of invasive factors, including MMP2 and MMP9, secreted by the HUVECs. We demonstrated significant suppression of tumor growth in a breast cancer xenograft model and enhanced distribution of HBP at the site of tumors. Taken together, our results show that HBP has antiangiogenic effects on ECs, and suggest that it may serve as a potential antitumor agent through control of the tumor microenvironment. Keywords: heparin-binding peptide, HBP, antiangiogenesis, heparan sulfate proteoglycans, HSPGs, endothelial cells, breast cancer xenograft, tumor microenvironment
format	article
author	Choi SH Lee JY Suh JS Park YS Chung CP Park YJ
author_facet	Choi SH Lee JY Suh JS Park YS Chung CP Park YJ
author_sort	Choi SH
title	Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
title_short	Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
title_full	Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
title_fullStr	Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
title_full_unstemmed	Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
title_sort	dual-function synthetic peptide derived from bmp4 for highly efficient tumor targeting and antiangiogenesis
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/3cb8f1019d67474fa94e8197c5685fb7
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Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis

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