Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization

Abstract The Apelin/APJ signalling pathway, involved in multiple physiological and pathological processes, has been attracting increasing interest recently. In our previous study, Apelin overexpression in colon26 tumor cells suppressed tumor growth by inducing vascular maturation. Here, we found tha...

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Autores principales:	Liuying Hu, Yumiko Hayashi, Hiroyasu Kidoya, Nobuyuki Takakura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4e8ea4612f98423499fc875b5a604869
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spelling	oai:doaj.org-article:4e8ea4612f98423499fc875b5a6048692021-12-02T16:14:46ZEndothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization10.1038/s41598-021-93619-52045-2322https://doaj.org/article/4e8ea4612f98423499fc875b5a6048692021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93619-5https://doaj.org/toc/2045-2322Abstract The Apelin/APJ signalling pathway, involved in multiple physiological and pathological processes, has been attracting increasing interest recently. In our previous study, Apelin overexpression in colon26 tumor cells suppressed tumor growth by inducing vascular maturation. Here, we found that MC38 and LLC tumor growth were greater in the absence of Apelin than in wild-type (WT) mice, suggesting that Apelin acts as a tumor suppressor. Consistent with this, treating WT mice with [Pyr1]Apelin-13 inhibited tumor growth. In MC38 tumors, only endothelial cells (ECs) strongly express APJ, a cognate receptor for Apelin, indicating that EC-derived Apelin might regulate tumor formation in an autocrine manner. Comparing with WT mice, larger numbers of vessels with narrower diameters were observed in tumors of Apelin knockout mice and lack of Apelin enhanced tumor hypoxia. Investigating immune cells in the tumor revealed that [Pyr1]Apelin-13 infusion induced the accumulation of CD8+ and CD4+ T cells in central areas. Moreover, RNA-sequencing analysis showed that Apelin induces chemokine CCL8 expression in ECs. Thus, enhancing anti-tumor immunity might be one of the mechanisms by which Apelin is involved in tumor growth. Our result indicated that increased CCL8 expression might induce CD8 + T cells infiltration into tumor and tumor inhibition.Liuying HuYumiko HayashiHiroyasu KidoyaNobuyuki TakakuraNature 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 Liuying Hu Yumiko Hayashi Hiroyasu Kidoya Nobuyuki Takakura Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization
description	Abstract The Apelin/APJ signalling pathway, involved in multiple physiological and pathological processes, has been attracting increasing interest recently. In our previous study, Apelin overexpression in colon26 tumor cells suppressed tumor growth by inducing vascular maturation. Here, we found that MC38 and LLC tumor growth were greater in the absence of Apelin than in wild-type (WT) mice, suggesting that Apelin acts as a tumor suppressor. Consistent with this, treating WT mice with [Pyr1]Apelin-13 inhibited tumor growth. In MC38 tumors, only endothelial cells (ECs) strongly express APJ, a cognate receptor for Apelin, indicating that EC-derived Apelin might regulate tumor formation in an autocrine manner. Comparing with WT mice, larger numbers of vessels with narrower diameters were observed in tumors of Apelin knockout mice and lack of Apelin enhanced tumor hypoxia. Investigating immune cells in the tumor revealed that [Pyr1]Apelin-13 infusion induced the accumulation of CD8+ and CD4+ T cells in central areas. Moreover, RNA-sequencing analysis showed that Apelin induces chemokine CCL8 expression in ECs. Thus, enhancing anti-tumor immunity might be one of the mechanisms by which Apelin is involved in tumor growth. Our result indicated that increased CCL8 expression might induce CD8 + T cells infiltration into tumor and tumor inhibition.
format	article
author	Liuying Hu Yumiko Hayashi Hiroyasu Kidoya Nobuyuki Takakura
author_facet	Liuying Hu Yumiko Hayashi Hiroyasu Kidoya Nobuyuki Takakura
author_sort	Liuying Hu
title	Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization
title_short	Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization
title_full	Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization
title_fullStr	Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization
title_full_unstemmed	Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization
title_sort	endothelial cell-derived apelin inhibits tumor growth by altering immune cell localization
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4e8ea4612f98423499fc875b5a604869
work_keys_str_mv	AT liuyinghu endothelialcellderivedapelininhibitstumorgrowthbyalteringimmunecelllocalization AT yumikohayashi endothelialcellderivedapelininhibitstumorgrowthbyalteringimmunecelllocalization AT hiroyasukidoya endothelialcellderivedapelininhibitstumorgrowthbyalteringimmunecelllocalization AT nobuyukitakakura endothelialcellderivedapelininhibitstumorgrowthbyalteringimmunecelllocalization
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Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization

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