Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway

Osteosarcoma is one of the most common primary malignant tumors of bone in adolescents. Human umbilical vein endothelial cells (HUVECs) derived exosomes are associated with osteosarcoma cell stemness. Little is known about the function of HUVECs-exosomes in osteosarcoma cell stemness. This work aime...

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Autores principales:	Jian Yang, Yong Hu, Lu Wang, Xiangran Sun, Ling Yu, Weichun Guo
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	human umbilical vein endothelial cells exosomes cell stemness notch signaling pathway osteosarcoma Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/cceeddbf717e44e4983e0139740ae9fa
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spelling	oai:doaj.org-article:cceeddbf717e44e4983e0139740ae9fa2021-12-01T14:41:00ZHuman umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway2165-59792165-598710.1080/21655979.2021.2005220https://doaj.org/article/cceeddbf717e44e4983e0139740ae9fa2021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2005220https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Osteosarcoma is one of the most common primary malignant tumors of bone in adolescents. Human umbilical vein endothelial cells (HUVECs) derived exosomes are associated with osteosarcoma cell stemness. Little is known about the function of HUVECs-exosomes in osteosarcoma cell stemness. This work aimed to investigate the mechanism of action of HUVECs-exosomes in regulating stem cell-like phenotypes of osteosarcoma cells. HUVECs were treated with GW4869 (exosome inhibitor). Human osteosarcoma cells (U2OS and 143B) were treated with HUVECs supernatant, HUVECs-exosomes with or without RO4929097 (γ secretase inhibitor, used to block Notch signaling pathway). We found that HUVECs supernatant and HUVECs-exosomes enhanced the proportions of STRO-1+CD117+ cells and the expression of stem cell-related proteins Oct4 and Sox2. Both HUVECs supernatant and HUVECs-exosomes promoted the sarcosphere formation efficiency of U2OS and 143B cells. These stem-like phenotypes of U2OS and 143B cells conferred by HUVECs-exosomes were repressed by GW4869. Moreover, HUVECs-exosomes promoted the expression of Notch1, Hes1 and Hey1 in the U2OS and 143B cells. RO4929097 treatment reversed the impact of HUVECs-exosomes on Notch1, Hes1, and Hey1 expression by inhibiting Notch1 signaling pathway. In conclusion, this work demonstrated that HUVECs-exosomes promoted cell stemness in osteosarcoma through activating Notch signaling pathway. Thus, our data reveal the mechanism of HUVECs-exosomes in regulating cell stemness of osteosarcoma, and provide a theoretical basis for osteosarcoma treatment by exosomes.Jian YangYong HuLu WangXiangran SunLing YuWeichun GuoTaylor & Francis Grouparticlehuman umbilical vein endothelial cellsexosomescell stemnessnotch signaling pathwayosteosarcomaBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 11007-11017 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human umbilical vein endothelial cells exosomes cell stemness notch signaling pathway osteosarcoma Biotechnology TP248.13-248.65
spellingShingle	human umbilical vein endothelial cells exosomes cell stemness notch signaling pathway osteosarcoma Biotechnology TP248.13-248.65 Jian Yang Yong Hu Lu Wang Xiangran Sun Ling Yu Weichun Guo Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway
description	Osteosarcoma is one of the most common primary malignant tumors of bone in adolescents. Human umbilical vein endothelial cells (HUVECs) derived exosomes are associated with osteosarcoma cell stemness. Little is known about the function of HUVECs-exosomes in osteosarcoma cell stemness. This work aimed to investigate the mechanism of action of HUVECs-exosomes in regulating stem cell-like phenotypes of osteosarcoma cells. HUVECs were treated with GW4869 (exosome inhibitor). Human osteosarcoma cells (U2OS and 143B) were treated with HUVECs supernatant, HUVECs-exosomes with or without RO4929097 (γ secretase inhibitor, used to block Notch signaling pathway). We found that HUVECs supernatant and HUVECs-exosomes enhanced the proportions of STRO-1+CD117+ cells and the expression of stem cell-related proteins Oct4 and Sox2. Both HUVECs supernatant and HUVECs-exosomes promoted the sarcosphere formation efficiency of U2OS and 143B cells. These stem-like phenotypes of U2OS and 143B cells conferred by HUVECs-exosomes were repressed by GW4869. Moreover, HUVECs-exosomes promoted the expression of Notch1, Hes1 and Hey1 in the U2OS and 143B cells. RO4929097 treatment reversed the impact of HUVECs-exosomes on Notch1, Hes1, and Hey1 expression by inhibiting Notch1 signaling pathway. In conclusion, this work demonstrated that HUVECs-exosomes promoted cell stemness in osteosarcoma through activating Notch signaling pathway. Thus, our data reveal the mechanism of HUVECs-exosomes in regulating cell stemness of osteosarcoma, and provide a theoretical basis for osteosarcoma treatment by exosomes.
format	article
author	Jian Yang Yong Hu Lu Wang Xiangran Sun Ling Yu Weichun Guo
author_facet	Jian Yang Yong Hu Lu Wang Xiangran Sun Ling Yu Weichun Guo
author_sort	Jian Yang
title	Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway
title_short	Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway
title_full	Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway
title_fullStr	Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway
title_full_unstemmed	Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway
title_sort	human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating notch signaling pathway
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/cceeddbf717e44e4983e0139740ae9fa
work_keys_str_mv	AT jianyang humanumbilicalveinendothelialcellsderivedexosomespromoteosteosarcomacellstemnessbyactivatingnotchsignalingpathway AT yonghu humanumbilicalveinendothelialcellsderivedexosomespromoteosteosarcomacellstemnessbyactivatingnotchsignalingpathway AT luwang humanumbilicalveinendothelialcellsderivedexosomespromoteosteosarcomacellstemnessbyactivatingnotchsignalingpathway AT xiangransun humanumbilicalveinendothelialcellsderivedexosomespromoteosteosarcomacellstemnessbyactivatingnotchsignalingpathway AT lingyu humanumbilicalveinendothelialcellsderivedexosomespromoteosteosarcomacellstemnessbyactivatingnotchsignalingpathway AT weichunguo humanumbilicalveinendothelialcellsderivedexosomespromoteosteosarcomacellstemnessbyactivatingnotchsignalingpathway
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Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway

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