title: Aminopeptidase N (APN/CD13) is selectively expressed in vascular endothelial cells and plays multiple roles in angiogenesis.
abstract: 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.
authors.affiliation: Evaluation Group, Biology Department, R & D Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd, 31-12 Shimo 3-Chome, Kita-Ku, Tokyo 115-8588, Japan. kazuteru.fukasawa@nipponkayaku.co.jp <kazuteru.fukasawa@nipponkayaku.co.jp>
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Fukasawa
authors.forename: Hideji
authors.initials: H
authors.lastname: Fujii
authors.forename: Yurika
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koizumi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Aozuka
authors.forename: Keiko
authors.initials: K
authors.lastname: Sekine
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yamada
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Nishikawa
mesh_terms: D018826:CD13 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002196:Capillaries / Q000378:metabolism / Q000502:physiology; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007797:Laminin / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D034741:RNA, Small Interfering; C059485:matrigel; D003094:Collagen; D018826:CD13 Antigens