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 trans-well 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.
Highlights
Endothelial progenitor cells (EPCs) are a subpopulation of mononuclear cells found in peripheral or cord blood
I The present study, we employed proteomics combined with glycoprotein enrichment to both outgrowth endothelial cells (OECs) and HUVECS to identify OEC cell surface markers and identified Nectin-2 as a surface marker that is highly expressed on OECs
Consecutive analysis showed that Nectin-2 co-localizes with common endothelial cell surface markers CD31, CD105, VE-Cadherin and CD146 (Fig 2E)
Summary
Endothelial progenitor cells (EPCs) are a subpopulation of mononuclear cells found in peripheral or cord blood. EPCs were first identified in 1997 [1]: the researchers described the isolation of CD34+ cells from human peripheral blood by using magnetic microbeads. Since this initial report, a number of groups have isolated EPCs from peripheral blood, bone marrow, fetal liver and umbilical cord blood. Previous studies used cell surface molecules such as CD34, CD133, VEGFR-2 (KDR/FLK-1/CD309), VE-Cadherin (CD144), Tie-2, etc., or combination of multiple molecules [2,3,4,5,6].
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