Nectin-2 (CD112) Is Expressed on Outgrowth Endothelial Cells and Regulates Cell Proliferation and Angiogenic Function
- Authors
- Son, YeonSung; Lee, BomNaeRin; Choi, Young-Jin; Jeon, Seon Ae; Kim, Ju-Hyun; Lee, Hoo-Keun; Kwon, Sang-Mo; Cho, Je-Yoel
- Issue Date
- 27-Sep-2016
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.11, no.9
- Journal Title
- PLOS ONE
- Volume
- 11
- Number
- 9
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7873
- DOI
- 10.1371/journal.pone.0163301
- ISSN
- 1932-6203
- Abstract
- Outgrowth endothelial cells (OECs) are a subpopulation of endothelial progenitor cells (EPCs) that have the capacity for proliferation and the ability to promote angiogenesis. In this study, we identified Nectin-2 as a surface protein of OECs through unbiased quantitative proteomics analysis. Using immunocytochemistry and flow cytometry, we confirmed that Nectin-2 is highly expressed on OECs. Nectin-2 (CD112) expression was limited or lower on mononuclear cells (MNCs) and mature tube-forming endothelial cells (ECs). Blocking Nectin-2 with a neutralizing monoclonal antibody significantly increased the transwell migration and tube forming capacity of OECs. Similarly, Nectin-2 knockdown resulted in enhanced tube formation, cell migration and proliferation with p-Erk activation. Moreover, Nectin-2 deficiency resulted in compensatory increase of other Nectin family genes including Nectin-3 and Necl-4 which promote VEGFR signaling. These results indicate that Nectin-2 is a surface marker and an important regulator of OECs, with significant implications for the isolation of OECs and blocking Nectin-2 on OECs by an antibody for angiogenic applications.
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