Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis

Abstract Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A3...

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Autores principales:	Judit Berta, Szilvia Török, Júlia Tárnoki-Zách, Orsolya Drozdovszky, József Tóvári, Sándor Paku, Ildikó Kovács, András Czirók, Bernard Masri, Zsolt Megyesfalvi, Henriett Oskolás, Johan Malm, Christian Ingvar, György Markó-Varga, Balázs Döme, Viktória László
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6db1b99335754b2f8199806375af0954
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spelling	oai:doaj.org-article:6db1b99335754b2f8199806375af09542021-12-02T15:53:58ZApelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis10.1038/s41598-021-85162-02045-2322https://doaj.org/article/6db1b99335754b2f8199806375af09542021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85162-0https://doaj.org/toc/2045-2322Abstract Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.Judit BertaSzilvia TörökJúlia Tárnoki-ZáchOrsolya DrozdovszkyJózsef TóváriSándor PakuIldikó KovácsAndrás CzirókBernard MasriZsolt MegyesfalviHenriett OskolásJohan MalmChristian IngvarGyörgy Markó-VargaBalázs DömeViktória LászlóNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Judit Berta Szilvia Török Júlia Tárnoki-Zách Orsolya Drozdovszky József Tóvári Sándor Paku Ildikó Kovács András Czirók Bernard Masri Zsolt Megyesfalvi Henriett Oskolás Johan Malm Christian Ingvar György Markó-Varga Balázs Döme Viktória László Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
description	Abstract Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.
format	article
author	Judit Berta Szilvia Török Júlia Tárnoki-Zách Orsolya Drozdovszky József Tóvári Sándor Paku Ildikó Kovács András Czirók Bernard Masri Zsolt Megyesfalvi Henriett Oskolás Johan Malm Christian Ingvar György Markó-Varga Balázs Döme Viktória László
author_facet	Judit Berta Szilvia Török Júlia Tárnoki-Zách Orsolya Drozdovszky József Tóvári Sándor Paku Ildikó Kovács András Czirók Bernard Masri Zsolt Megyesfalvi Henriett Oskolás Johan Malm Christian Ingvar György Markó-Varga Balázs Döme Viktória László
author_sort	Judit Berta
title	Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
title_short	Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
title_full	Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
title_fullStr	Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
title_full_unstemmed	Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
title_sort	apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6db1b99335754b2f8199806375af0954
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Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis

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