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N-Acetylglucosaminyltransferase V Regulates Extravillous Trophoblast Invasion through Glycosylation of 5β1 Integrin

Departments of Obstetrics and Gynecology (E.Y., K.Ino, S.S., A.I., H.K., K.S., A.N., F.K.) and Hematology (A.A.), Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan; and Departments of Molecular Biochemistry and Clinical Investigation (E.M.) and Biochemistry (E.M., K.Ina.), Osaka University Graduate School of Medicine, 565-0871 Suita, Japan

Address all correspondence and requests for reprints to: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: yamaeiko{at}med.nagoya-u.ac.jp.

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 β1, 6-N-acetylglucosamine (β1-6GlcNAc) branching on asparagine-linked oligosaccharides of cell proteins. GnT-V and its product, β1-6GlcNAc, 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-V in 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 β1-6GlcNAc 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 β1-6 branching of 5β1 integrin was significantly reduced in small interfering GnT-V-transfected Jar cells compared with mock transfectants, although the expression of 1, 5, 6, and β1 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 5β1 integrin.

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