N-Acetylglucosaminyltransferase V Regulates Extravillous Trophoblast Invasion through Glycosylation of α5β1 Integrin

被引:34
|
作者
Yamamoto, Eiko [1 ]
Ino, Kazuhiko
Miyoshi, Eiji [3 ,4 ]
Inamori, Kei-ichiro [4 ]
Abe, Akihiro [2 ]
Sumigama, Seiji
Iwase, Akira
Kajiyama, Hiroaki
Shibata, Kiyosumi
Nawa, Akihiro
Kikkawa, Fumitaka
机构
[1] Nagoya Univ, Grad Sch Med, Dept Obstet & Gynecol, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Hematol, Nagoya, Aichi 4668550, Japan
[3] Osaka Univ, Grad Sch Med, Dept Mol Biochem & Clin Invest, Suita, Osaka 5650871, Japan
[4] Osaka Univ, Grad Sch Med, Dept Biochem, Suita, Osaka 5650871, Japan
关键词
GROWTH-FACTOR-BETA; CELL-MIGRATION; POOR-PROGNOSIS; HUMAN PLACENTA; EXPRESSION; ADHESION; GLYCOPROTEINS; PHENOTYPES; OLIGOSACCHARIDES; TRANSCRIPTION;
D O I
10.1210/en.2008-1005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
For successful human placentation, invasion of trophoblast cells into the uterus and its associated vasculature is essential, and the regulation of this process is controlled by many factors at the fetal-maternal interface. N-acetylglucosaminyltransferase V (GnT-V) is a key enzyme that catalyzes beta 1, 6-N-acetylglucosamine (beta 1-6GlcNAc) branching on asparagine-linked oligosaccharides of cell proteins. GnT-V and its product, beta 1-6GlcNAc, are known to regulate cellular transformation and correlate with the metastatic potential of various cancer cells. The aim of the present study was to determine whether extravillous trophoblast (EVT) expressed this molecule and examine the role of GnT-Vin the regulation of human trophoblast invasion. Immunohistochemistry showed that GnT-V was strongly expressed within the cytoplasm of EVT in the anchoring villi; this expression was down-regulated in EVTs invading the decidua. Suppression of beta 1-6GlcNAc glycosylation by swainsonine enhanced the migratory potential and invasive capability of both primary EVTs and the EVT cell line, HTR-8/SVneo. Down-regulation of GnT-V expression by small interfering RNA in the choriocarcinoma cell line Jar consistently enhanced the migration and invasive capacity of these cells and elevated cellular adhesion to extracellular matrix proteins, such as fibronectin and collagen type I/IV. The extent of beta 1-6 branching of alpha 5 beta 1 integrin was significantly reduced in small interfering GnT-V-transfected Jar cells compared with mock transfectants, although the expression of alpha 1, alpha 5, alpha 6, and beta 1 integrin on the cell surface was not changed. These results suggest that GnT-V is expressed in human EVT and is involved in regulating trophoblast invasion through modifications of the oligosaccharide chains of alpha 5 beta 1 integrin. (Endocrinology 150: 990-999, 2009)
引用
收藏
页码:990 / 999
页数:10
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