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 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 Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Choi SH [verfasserIn] Lee JY [verfasserIn] Suh JS [verfasserIn] Park YS [verfasserIn] Chung CP [verfasserIn] Park YJ [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2016

Schlagwörter:	Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment

Übergeordnetes Werk:	In: International Journal of Nanomedicine - Dove Medical Press, 2018, (2016), Seite 4643-4656
Übergeordnetes Werk:	year:2016 ; pages:4643-4656

Links:	Link aufrufen Link aufrufen Journal toc

Katalog-ID:	DOAJ060479221

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allfields	(DE-627)DOAJ060479221 (DE-599)DOAJ3cb8f1019d67474fa94e8197c5685fb7 DE-627 ger DE-627 rakwb eng R5-920 Choi SH verfasserin aut Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment Medicine (General) Lee JY verfasserin aut Suh JS verfasserin aut Park YS verfasserin aut Chung CP verfasserin aut Park YJ verfasserin aut In International Journal of Nanomedicine Dove Medical Press, 2018 (2016), Seite 4643-4656 (DE-627)537879560 (DE-600)2377464-2 11782013 nnns year:2016 pages:4643-4656 https://doaj.org/article/3cb8f1019d67474fa94e8197c5685fb7 kostenfrei https://www.dovepress.com/dual-function-synthetic-peptide-derived-from-bmp4-for-highly-efficient-peer-reviewed-article-IJN kostenfrei https://doaj.org/toc/1178-2013 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2016 4643-4656
spelling	(DE-627)DOAJ060479221 (DE-599)DOAJ3cb8f1019d67474fa94e8197c5685fb7 DE-627 ger DE-627 rakwb eng R5-920 Choi SH verfasserin aut Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment Medicine (General) Lee JY verfasserin aut Suh JS verfasserin aut Park YS verfasserin aut Chung CP verfasserin aut Park YJ verfasserin aut In International Journal of Nanomedicine Dove Medical Press, 2018 (2016), Seite 4643-4656 (DE-627)537879560 (DE-600)2377464-2 11782013 nnns year:2016 pages:4643-4656 https://doaj.org/article/3cb8f1019d67474fa94e8197c5685fb7 kostenfrei https://www.dovepress.com/dual-function-synthetic-peptide-derived-from-bmp4-for-highly-efficient-peer-reviewed-article-IJN kostenfrei https://doaj.org/toc/1178-2013 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2016 4643-4656
allfields_unstemmed	(DE-627)DOAJ060479221 (DE-599)DOAJ3cb8f1019d67474fa94e8197c5685fb7 DE-627 ger DE-627 rakwb eng R5-920 Choi SH verfasserin aut Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment Medicine (General) Lee JY verfasserin aut Suh JS verfasserin aut Park YS verfasserin aut Chung CP verfasserin aut Park YJ verfasserin aut In International Journal of Nanomedicine Dove Medical Press, 2018 (2016), Seite 4643-4656 (DE-627)537879560 (DE-600)2377464-2 11782013 nnns year:2016 pages:4643-4656 https://doaj.org/article/3cb8f1019d67474fa94e8197c5685fb7 kostenfrei https://www.dovepress.com/dual-function-synthetic-peptide-derived-from-bmp4-for-highly-efficient-peer-reviewed-article-IJN kostenfrei https://doaj.org/toc/1178-2013 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2016 4643-4656
allfieldsGer	(DE-627)DOAJ060479221 (DE-599)DOAJ3cb8f1019d67474fa94e8197c5685fb7 DE-627 ger DE-627 rakwb eng R5-920 Choi SH verfasserin aut Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment Medicine (General) Lee JY verfasserin aut Suh JS verfasserin aut Park YS verfasserin aut Chung CP verfasserin aut Park YJ verfasserin aut In International Journal of Nanomedicine Dove Medical Press, 2018 (2016), Seite 4643-4656 (DE-627)537879560 (DE-600)2377464-2 11782013 nnns year:2016 pages:4643-4656 https://doaj.org/article/3cb8f1019d67474fa94e8197c5685fb7 kostenfrei https://www.dovepress.com/dual-function-synthetic-peptide-derived-from-bmp4-for-highly-efficient-peer-reviewed-article-IJN kostenfrei https://doaj.org/toc/1178-2013 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2016 4643-4656
allfieldsSound	(DE-627)DOAJ060479221 (DE-599)DOAJ3cb8f1019d67474fa94e8197c5685fb7 DE-627 ger DE-627 rakwb eng R5-920 Choi SH verfasserin aut Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment Medicine (General) Lee JY verfasserin aut Suh JS verfasserin aut Park YS verfasserin aut Chung CP verfasserin aut Park YJ verfasserin aut In International Journal of Nanomedicine Dove Medical Press, 2018 (2016), Seite 4643-4656 (DE-627)537879560 (DE-600)2377464-2 11782013 nnns year:2016 pages:4643-4656 https://doaj.org/article/3cb8f1019d67474fa94e8197c5685fb7 kostenfrei https://www.dovepress.com/dual-function-synthetic-peptide-derived-from-bmp4-for-highly-efficient-peer-reviewed-article-IJN kostenfrei https://doaj.org/toc/1178-2013 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2016 4643-4656
language	English
source	In International Journal of Nanomedicine (2016), Seite 4643-4656 year:2016 pages:4643-4656
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topic_facet	Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment Medicine (General)
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authorswithroles_txt_mv	Choi SH @@aut@@ Lee JY @@aut@@ Suh JS @@aut@@ Park YS @@aut@@ Chung CP @@aut@@ Park YJ @@aut@@
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spellingShingle	Choi SH misc R5-920 misc Heparin binding peptide (HBP) misc anti-angiogenesis misc heparan sulfate proteoglycans (HSPGs) misc endothelial cells misc breast cancer xenograft misc tumor microenvironment misc Medicine (General) Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
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topic_title	R5-920 Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis Heparin binding peptide (HBP) anti-angiogenesis heparan sulfate proteoglycans (HSPGs) endothelial cells breast cancer xenograft tumor microenvironment
topic	misc R5-920 misc Heparin binding peptide (HBP) misc anti-angiogenesis misc heparan sulfate proteoglycans (HSPGs) misc endothelial cells misc breast cancer xenograft misc tumor microenvironment misc Medicine (General)
topic_unstemmed	misc R5-920 misc Heparin binding peptide (HBP) misc anti-angiogenesis misc heparan sulfate proteoglycans (HSPGs) misc endothelial cells misc breast cancer xenograft misc tumor microenvironment misc Medicine (General)
topic_browse	misc R5-920 misc Heparin binding peptide (HBP) misc anti-angiogenesis misc heparan sulfate proteoglycans (HSPGs) misc endothelial cells misc breast cancer xenograft misc tumor microenvironment misc Medicine (General)
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title	Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
ctrlnum	(DE-627)DOAJ060479221 (DE-599)DOAJ3cb8f1019d67474fa94e8197c5685fb7
title_full	Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
author_sort	Choi SH
journal	International Journal of Nanomedicine
journalStr	International Journal of Nanomedicine
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author_browse	Choi SH Lee JY Suh JS Park YS Chung CP Park YJ
class	R5-920
format_se	Elektronische Aufsätze
author-letter	Choi SH
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title_sort	dual-function synthetic peptide derived from bmp4 for highly efficient tumor targeting and antiangiogenesis
callnumber	R5-920
title_auth	Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
abstract	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
abstractGer	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
abstract_unstemmed	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
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title_short	Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis
url	https://doaj.org/article/3cb8f1019d67474fa94e8197c5685fb7 https://www.dovepress.com/dual-function-synthetic-peptide-derived-from-bmp4-for-highly-efficient-peer-reviewed-article-IJN https://doaj.org/toc/1178-2013
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up_date	2024-07-03T15:12:43.443Z
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