REG3β modifies cell tumor function by impairing extracellular vesicle uptake

Abstract Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-sized membrane vesicles containing proteins and nucleic acids, which act as intercellular messengers. They play an important role in a variety of physiological processes, as well as in pathological situations such...

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Autores principales:	Laia Bonjoch, Meritxell Gironella, Juan Lucio Iovanna, Daniel Closa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/18aa00ec6b494d09b82b1dba44412178
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spelling	oai:doaj.org-article:18aa00ec6b494d09b82b1dba444121782021-12-02T12:30:25ZREG3β modifies cell tumor function by impairing extracellular vesicle uptake10.1038/s41598-017-03244-42045-2322https://doaj.org/article/18aa00ec6b494d09b82b1dba444121782017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03244-4https://doaj.org/toc/2045-2322Abstract Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-sized membrane vesicles containing proteins and nucleic acids, which act as intercellular messengers. They play an important role in a variety of physiological processes, as well as in pathological situations such as inflammation or cancer. Here, we show that in the case of pancreatic ductal adenocarcinoma (PDAC), the healthy pancreatic tissue surrounding the tumor releases REG3β, a lectin that binds to the glycoproteins present in the surface of EVs, thus interfering with their uptake and internalization by target cells. In vitro, the disruption of the signaling mediated by EVs due to the presence of REG3β, prevents the EV-induced phenotypic switch in macrophages, inhibits the increased cell migration of cancer cells and reverses a number of metabolomic changes promoted by EVs. In vivo, the uptake of REG3β+ EVs by tumor cells is significantly impaired. Furthermore, it results in an increase of circulating REG3β+ EVs in blood of pancreatic cancer patients. Our findings highlight the effect of a lectin released by the healthy pancreatic tissue surrounding the tumor in modulating the EV-mediated interactions between different cell types in PDAC.Laia BonjochMeritxell GironellaJuan Lucio IovannaDaniel ClosaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laia Bonjoch Meritxell Gironella Juan Lucio Iovanna Daniel Closa REG3β modifies cell tumor function by impairing extracellular vesicle uptake
description	Abstract Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-sized membrane vesicles containing proteins and nucleic acids, which act as intercellular messengers. They play an important role in a variety of physiological processes, as well as in pathological situations such as inflammation or cancer. Here, we show that in the case of pancreatic ductal adenocarcinoma (PDAC), the healthy pancreatic tissue surrounding the tumor releases REG3β, a lectin that binds to the glycoproteins present in the surface of EVs, thus interfering with their uptake and internalization by target cells. In vitro, the disruption of the signaling mediated by EVs due to the presence of REG3β, prevents the EV-induced phenotypic switch in macrophages, inhibits the increased cell migration of cancer cells and reverses a number of metabolomic changes promoted by EVs. In vivo, the uptake of REG3β+ EVs by tumor cells is significantly impaired. Furthermore, it results in an increase of circulating REG3β+ EVs in blood of pancreatic cancer patients. Our findings highlight the effect of a lectin released by the healthy pancreatic tissue surrounding the tumor in modulating the EV-mediated interactions between different cell types in PDAC.
format	article
author	Laia Bonjoch Meritxell Gironella Juan Lucio Iovanna Daniel Closa
author_facet	Laia Bonjoch Meritxell Gironella Juan Lucio Iovanna Daniel Closa
author_sort	Laia Bonjoch
title	REG3β modifies cell tumor function by impairing extracellular vesicle uptake
title_short	REG3β modifies cell tumor function by impairing extracellular vesicle uptake
title_full	REG3β modifies cell tumor function by impairing extracellular vesicle uptake
title_fullStr	REG3β modifies cell tumor function by impairing extracellular vesicle uptake
title_full_unstemmed	REG3β modifies cell tumor function by impairing extracellular vesicle uptake
title_sort	reg3β modifies cell tumor function by impairing extracellular vesicle uptake
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/18aa00ec6b494d09b82b1dba44412178
work_keys_str_mv	AT laiabonjoch reg3bmodifiescelltumorfunctionbyimpairingextracellularvesicleuptake AT meritxellgironella reg3bmodifiescelltumorfunctionbyimpairingextracellularvesicleuptake AT juanlucioiovanna reg3bmodifiescelltumorfunctionbyimpairingextracellularvesicleuptake AT danielclosa reg3bmodifiescelltumorfunctionbyimpairingextracellularvesicleuptake
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REG3β modifies cell tumor function by impairing extracellular vesicle uptake

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