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Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis

Authors :
Peng Ye
Zelong Fu
Jeff Yat-Fai Chung
Xiaoyun Cao
Ho Ko
Xiao Yu Tian
Patrick Ming-Kuen Tang
Kathy O. Lui
Source :
Frontiers in Cardiovascular Medicine, Vol 8 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

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.

Details

Language :
English
ISSN :
2297055X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
Frontiers in Cardiovascular Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.5a4df317ce26489699f56fb4a3f063ba
Document Type :
article
Full Text :
https://doi.org/10.3389/fcvm.2021.810477