ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs

Abstract Tumor-associated lymphatic vessels (LV) serve as a route of cancer dissemination through the prometastatic crosstalk between lymphatic endothelial cells (LECs) lining the LVs and cancer cells. Compared to blood endothelial cell-derived angiocrine factors, however, LEC-secreted factors in th...

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Autores principales:	Kwang-Soo Kim, Ji-In Park, Nuri Oh, Hyeon-Ju Cho, Ji-Hoon Park, Kyung-Soon Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83ac7a0c2f854ec6a6e2c38717e641dc
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spelling	oai:doaj.org-article:83ac7a0c2f854ec6a6e2c38717e641dc2021-12-02T15:09:21ZELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs10.1038/s41598-019-44828-62045-2322https://doaj.org/article/83ac7a0c2f854ec6a6e2c38717e641dc2019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-44828-6https://doaj.org/toc/2045-2322Abstract Tumor-associated lymphatic vessels (LV) serve as a route of cancer dissemination through the prometastatic crosstalk between lymphatic endothelial cells (LECs) lining the LVs and cancer cells. Compared to blood endothelial cell-derived angiocrine factors, however, LEC-secreted factors in the tumor microenvironment and their roles in tumor metastasis are poorly understood. Here, we report that ELK3 expressed in LECs contributes to the dissemination of cancer cells during tumor growth by providing oncogenic miRNAs to tumor cells through exosomes. We found that conditioned medium from ELK3-suppressed LECs (LCM) lost its ability to promote the migration and invasion of breast cancer cells such as MDA-MB-231, Hs578T and BT20 in vitro. Suppression of ELK3 in LECs diminished the ability of LECs to promote tumor growth and metastasis of MDA-MB-231 in vivo. Exosomes derived from LECs significantly increased the migration and invasion of MDA-MB-231 in vitro, but ELK3 suppression significantly diminished the pro-oncogenic activity of exosomes from LECs. Based on the miRNA expression profiles of LECs and functional analysis, we identified miR-503-3p, miR-4269 and miR-30e-3p as downstream targets of ELK3 in LECs, which cause the above phenotype of cancer cells. These findings strongly suggest that ELK3 expressed in LECs is a major regulator that controls the communication between the tumor microenvironment and tumors to support cancer metastasis.Kwang-Soo KimJi-In ParkNuri OhHyeon-Ju ChoJi-Hoon ParkKyung-Soon ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kwang-Soo Kim Ji-In Park Nuri Oh Hyeon-Ju Cho Ji-Hoon Park Kyung-Soon Park ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs
description	Abstract Tumor-associated lymphatic vessels (LV) serve as a route of cancer dissemination through the prometastatic crosstalk between lymphatic endothelial cells (LECs) lining the LVs and cancer cells. Compared to blood endothelial cell-derived angiocrine factors, however, LEC-secreted factors in the tumor microenvironment and their roles in tumor metastasis are poorly understood. Here, we report that ELK3 expressed in LECs contributes to the dissemination of cancer cells during tumor growth by providing oncogenic miRNAs to tumor cells through exosomes. We found that conditioned medium from ELK3-suppressed LECs (LCM) lost its ability to promote the migration and invasion of breast cancer cells such as MDA-MB-231, Hs578T and BT20 in vitro. Suppression of ELK3 in LECs diminished the ability of LECs to promote tumor growth and metastasis of MDA-MB-231 in vivo. Exosomes derived from LECs significantly increased the migration and invasion of MDA-MB-231 in vitro, but ELK3 suppression significantly diminished the pro-oncogenic activity of exosomes from LECs. Based on the miRNA expression profiles of LECs and functional analysis, we identified miR-503-3p, miR-4269 and miR-30e-3p as downstream targets of ELK3 in LECs, which cause the above phenotype of cancer cells. These findings strongly suggest that ELK3 expressed in LECs is a major regulator that controls the communication between the tumor microenvironment and tumors to support cancer metastasis.
format	article
author	Kwang-Soo Kim Ji-In Park Nuri Oh Hyeon-Ju Cho Ji-Hoon Park Kyung-Soon Park
author_facet	Kwang-Soo Kim Ji-In Park Nuri Oh Hyeon-Ju Cho Ji-Hoon Park Kyung-Soon Park
author_sort	Kwang-Soo Kim
title	ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs
title_short	ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs
title_full	ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs
title_fullStr	ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs
title_full_unstemmed	ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs
title_sort	elk3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal mirnas
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/83ac7a0c2f854ec6a6e2c38717e641dc
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ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs

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