Nectin-2 (CD112) Is Expressed on Outgrowth Endothelial Cells and Regulates Cell Proliferation and Angiogenic Function.
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.
Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea.
YeonSung
Y
Son
Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea.
BomNaeRin
B
Lee
Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea.
Young-Jin
YJ
Choi
Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea.
Seon Ae
SA
Jeon
Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea.
Ju-Hyun
JH
Kim
College of Pharmacy, Gachon University, Incheon 406-840, Republic of Korea.
Hoo-Keun
HK
Lee
Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, school of Medicine, Pusan National University, Yangsan, 626-870 Korea.
Sang-Mo
SM
Kwon
Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea.
Je-Yoel
JY
Cho
Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1442-7
15191940
Blood. 2000 Feb 1;95(3):952-8
10648408
J Cell Sci. 2008 Jun 15;121(Pt 12):2008-17
18505795
Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):223-32
18162609
Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1584-95
18669889
Circ Res. 2010 Jun 11;106(11):1731-42
20413783
J Biol Chem. 2011 Oct 21;286(42):36297-303
21880730
PLoS One. 2013 Oct 07;8(10):e77424
24116228
Cardiovasc Res. 2013 Apr 1;98(1):73-82
23386276
Science. 1997 Feb 14;275(5302):964-7
9020076
Circ Res. 2006 Mar 31;98(6):743-56
16574915
Circulation. 2002 Nov 26;106(22):2781-6
12451003
Curr Opin Cell Biol. 2007 Oct;19(5):593-602
17942295
PLoS One. 2015 Apr 20;10 (4):e0124259
25893857
Nat Rev Mol Cell Biol. 2008 Aug;9(8):603-15
18648374
Int Immunol. 2004 Apr;16(4):533-8
15039383
Blood. 1998 Dec 15;92(12):4602-11
9845526
Genes Cells. 2006 Sep;11(9):1125-32
16923130
Circ Res. 2012 Mar 2;110(5):716-26
22282193
J Immunol. 2012 Jun 1;188(11):5511-20
22547693
J Clin Invest. 2000 Jan;105(1):71-7
10619863
Cancer Res. 2000 Jan 15;60(2):203-12
10667560
J Cell Biol. 2006 Aug 14;174(4):593-604
16893970
Circ Res. 2001 Jul 6;89(1):E1-7
11440984
Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):288-93
14699017
Circ Res. 2009 Apr 24;104(8):969-77
19325148
Blood. 1997 Dec 15;90(12):5002-12
9389720
Microvasc Res. 2010 Dec;80(3):317-23
20594997
J Cell Biol. 2005 Oct 10;171(1):165-73
16216929
Invest Ophthalmol Vis Sci. 2010 Nov;51(11):5906-13
20554606
J Exp Med. 2003 Aug 18;198(4):557-67
12913096