Aminopeptidase N (APN/CD13) is selectively expressed in vascular endothelial cells and plays multiple roles in angiogenesis

被引:134
作者
Fukasawa, Kazuteru
Fujii, Hideji
Saitoh, Yurika
Koizumi, Keiichi
Aozuka, Yasushi
Sekine, Keiko
Yamada, Masatoshi
Saiki, Ikuo
Nishikawa, Kiyohiro
机构
[1] Nippon Kayaku Co Ltd, Pharmaceut Grp, R&D Div, Evaluat Grp,Biol Dept,Kita Ku, Tokyo 1158588, Japan
[2] Toyama Med & Pharmaceut Univ, Inst Nat Med, Dept Biosci, Div Pathogen Biochem, Toyama 9300194, Japan
[3] Toyama Med & Pharmaceut Univ, Century COE Program 21, Toyama 9300194, Japan
关键词
aminopeptidase N (APN/CD13); angiogenesis; vascular endothelial cells; tube-like structure; adhesion;
D O I
10.1016/j.canlet.2005.11.051
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Proteolytic enzyme-mediated degradation of the extracellular matrix (ECM) is crucial for the formation of both tumor metastasis and angiogenesis. Recently, several reports have suggested that aminopeptidases are involved in this process, but precisely how is largely unknown. We found here that aminopeptidase N (APN/CD13) was selectively expressed in vascular endothelial cells including human umbilical vein endothelial cells (HUVEC) and human aortic endothelial cells (HAEC), and was not detectable in a majority of normal cells and tumor cell lines we examined. RNA interference (RNAi) of APN resulted in the inhibition of capillary tube formation of HUVEC on Matrigel. APN siRNA suppressed the migration of HUVEC through a fibronectin-coated Transwell membrane, and reduced the cellular adhesion to Matrigel and various adhesion molecules including type IV collagen, type I collagen and fibronectin. These findings suggest that APN is a multifunctional protein with important roles in vascular endothelial morphogenesis during angiogenesis. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:135 / 143
页数:9
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