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Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis

Recently, the extracellular matrix protein agrin has been reported to promote tumor angiogenesis that supports tumorigenesis and metastasis; however, there is a lack of in vivo genetic evidence to prove whether agrin derived from the tumors or endothelial cells (ECs) systemically should be the thera...

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Autores principales: Ye, Peng, Fu, Zelong, Chung, Jeff Yat-Fai, Cao, Xiaoyun, Ko, Ho, Tian, Xiao Yu, Tang, Patrick Ming-Kuen, Lui, Kathy O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841877/
https://www.ncbi.nlm.nih.gov/pubmed/35174224
http://dx.doi.org/10.3389/fcvm.2021.810477
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author Ye, Peng
Fu, Zelong
Chung, Jeff Yat-Fai
Cao, Xiaoyun
Ko, Ho
Tian, Xiao Yu
Tang, Patrick Ming-Kuen
Lui, Kathy O.
author_facet Ye, Peng
Fu, Zelong
Chung, Jeff Yat-Fai
Cao, Xiaoyun
Ko, Ho
Tian, Xiao Yu
Tang, Patrick Ming-Kuen
Lui, Kathy O.
author_sort Ye, Peng
collection PubMed
description Recently, the extracellular matrix protein agrin has been reported to promote tumor angiogenesis that supports tumorigenesis and metastasis; however, there is a lack of in vivo genetic evidence to prove whether agrin derived from the tumors or endothelial cells (ECs) systemically should be the therapeutic target. To date, the physiological role of endothelial agrin has also not been investigated. In the EC-specific agrin knockout mice, we observed normal endothelial and haematopoietic cell development during embryogenesis. Moreover, these mice develop normal vascular barrier integrity and vasoreactivity at the adult stage. Importantly, the growth of localized or metastatic cancer cells was not affected after implantation into endothelial agrin depleted mice. Mechanistically, agrin did not regulate endothelial ERK1/2, YAP or p53 activation in vivo that is central to support endothelial proliferation, survival and invasion. Cumulatively, our findings may suggest that agrin could play a redundant role in endothelial development during physiological and tumor angiogenesis. Targeting the endothelial derived agrin might not be effective in inhibiting tumor angiogenesis.
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spelling pubmed-88418772022-02-15 Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis Ye, Peng Fu, Zelong Chung, Jeff Yat-Fai Cao, Xiaoyun Ko, Ho Tian, Xiao Yu Tang, Patrick Ming-Kuen Lui, Kathy O. Front Cardiovasc Med Cardiovascular Medicine Recently, the extracellular matrix protein agrin has been reported to promote tumor angiogenesis that supports tumorigenesis and metastasis; however, there is a lack of in vivo genetic evidence to prove whether agrin derived from the tumors or endothelial cells (ECs) systemically should be the therapeutic target. To date, the physiological role of endothelial agrin has also not been investigated. In the EC-specific agrin knockout mice, we observed normal endothelial and haematopoietic cell development during embryogenesis. Moreover, these mice develop normal vascular barrier integrity and vasoreactivity at the adult stage. Importantly, the growth of localized or metastatic cancer cells was not affected after implantation into endothelial agrin depleted mice. Mechanistically, agrin did not regulate endothelial ERK1/2, YAP or p53 activation in vivo that is central to support endothelial proliferation, survival and invasion. Cumulatively, our findings may suggest that agrin could play a redundant role in endothelial development during physiological and tumor angiogenesis. Targeting the endothelial derived agrin might not be effective in inhibiting tumor angiogenesis. Frontiers Media S.A. 2022-01-31 /pmc/articles/PMC8841877/ /pubmed/35174224 http://dx.doi.org/10.3389/fcvm.2021.810477 Text en Copyright © 2022 Ye, Fu, Chung, Cao, Ko, Tian, Tang and Lui. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Ye, Peng
Fu, Zelong
Chung, Jeff Yat-Fai
Cao, Xiaoyun
Ko, Ho
Tian, Xiao Yu
Tang, Patrick Ming-Kuen
Lui, Kathy O.
Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis
title Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis
title_full Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis
title_fullStr Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis
title_full_unstemmed Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis
title_short Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis
title_sort endothelial agrin is dispensable for normal and tumor angiogenesis
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841877/
https://www.ncbi.nlm.nih.gov/pubmed/35174224
http://dx.doi.org/10.3389/fcvm.2021.810477
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