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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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.810477/full |
| _version_ | 1798024738129313792 |
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| author | Peng Ye Zelong Fu Jeff Yat-Fai Chung Xiaoyun Cao Ho Ko Ho Ko Xiao Yu Tian Patrick Ming-Kuen Tang Kathy O. Lui Kathy O. Lui Kathy O. Lui |
| author_facet | Peng Ye Zelong Fu Jeff Yat-Fai Chung Xiaoyun Cao Ho Ko Ho Ko Xiao Yu Tian Patrick Ming-Kuen Tang Kathy O. Lui Kathy O. Lui Kathy O. Lui |
| author_sort | Peng Ye |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T18:07:30Z |
| format | Article |
| id | doaj.art-5a4df317ce26489699f56fb4a3f063ba |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-11T18:07:30Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-5a4df317ce26489699f56fb4a3f063ba2022-12-22T04:10:17ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-01-01810.3389/fcvm.2021.810477810477Endothelial Agrin Is Dispensable for Normal and Tumor AngiogenesisPeng Ye0Zelong Fu1Jeff Yat-Fai Chung2Xiaoyun Cao3Ho Ko4Ho Ko5Xiao Yu Tian6Patrick Ming-Kuen Tang7Kathy O. Lui8Kathy O. Lui9Kathy O. Lui10Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, ChinaState Key Laboratory of Translational Oncology, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, ChinaLi Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaState Key Laboratory of Translational Oncology, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, ChinaLi Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, ChinaShenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, ChinaRecently, 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.https://www.frontiersin.org/articles/10.3389/fcvm.2021.810477/fullagrinendothelial cell (EC)angiogenesistumorigenesismetastasis |
| spellingShingle | Peng Ye Zelong Fu Jeff Yat-Fai Chung Xiaoyun Cao Ho Ko Ho Ko Xiao Yu Tian Patrick Ming-Kuen Tang Kathy O. Lui Kathy O. Lui Kathy O. Lui Endothelial Agrin Is Dispensable for Normal and Tumor Angiogenesis Frontiers in Cardiovascular Medicine agrin endothelial cell (EC) angiogenesis tumorigenesis metastasis |
| 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 | agrin endothelial cell (EC) angiogenesis tumorigenesis metastasis |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.810477/full |
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