282 EXPRESSION OF LAMININ-BINDING GLYCANS ON α-DYSTROGLYCAN CORRELATES WITH TUMOR SUPPRESSOR FUNCTION IN PROSTATE CANCER (2011)

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011282 EXPRESSION OF LAMININ-BINDING GLYCANS ON α-DYSTROGLYCAN CORRELATES WITH TUMOR SUPPRESSOR FUNCTION IN PROSTATE CANCER Shingo Hatakeyama, Xingfeng Bao, Noriko Tokui, Teppei Okamoto, Kengo Imanishi, Yusuke Ishibashi, Hiromi Murasawa, Yuichiro Suzuki, Naoki Sugiyama, Hayato Yamamoto, Shigemasa Kudo, Takahiro Yoneyama, Takuya Koie, Noritaka Kamimura, Minoru Fukuda, and Chikara Ohyama Shingo HatakeyamaShingo Hatakeyama Hirosaki, Japan More articles by this author , Xingfeng BaoXingfeng Bao La Jolla, CA More articles by this author , Noriko TokuiNoriko Tokui Hirosaki, Japan More articles by this author , Teppei OkamotoTeppei Okamoto Hirosaki, Japan More articles by this author , Kengo ImanishiKengo Imanishi Hirosaki, Japan More articles by this author , Yusuke IshibashiYusuke Ishibashi Hirosaki, Japan More articles by this author , Hiromi MurasawaHiromi Murasawa Hirosaki, Japan More articles by this author , Yuichiro SuzukiYuichiro Suzuki Hirosaki, Japan More articles by this author , Naoki SugiyamaNaoki Sugiyama Hirosaki, Japan More articles by this author , Hayato YamamotoHayato Yamamoto Hirosaki, Japan More articles by this author , Shigemasa KudoShigemasa Kudo Hirosaki, Japan More articles by this author , Takahiro YoneyamaTakahiro Yoneyama Hirosaki, Japan More articles by this author , Takuya KoieTakuya Koie Hirosaki, Japan More articles by this author , Noritaka KamimuraNoritaka Kamimura Hirosaki, Japan More articles by this author , Minoru FukudaMinoru Fukuda La Jolla, CA More articles by this author , and Chikara OhyamaChikara Ohyama Hirosaki, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.374AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Alpha-dystroglycan (α-DG) represents a highly glycosylated cell surface molecule that is expressed in the epithelial cell-basement membrane (BM) interface and plays an essential role in epithelium development and tissue organization. Despite the critical function of α-DG glycosylation in the muscular system, not much is known about cancer development. Several reports have shown that defects in α-DG are associated with breast, colon, oral, and prostate carcinomas. However, the molecular cause for the α-DG defects in carcinomas and the mechanistic link between α-DG defects and tumor progression are not known. We report here a suppressor function of laminin-binding glycans on α-DG in prostate cancer. METHODS To determine whether the loss of laminin-binding glycans or loss of α-DG core protein is associated with tumor progression, we examined the expression of α-DG core protein and its glycosylation in normal and carcinoma of human prostate by immunohistochemistry. PC3 cells were separated into those expressing substantial (PC3-H) and minimal (PC3-L) amounts of laminin-binding glycans. Laminin-binding assay in PC3-H was performed to confirm the interaction between α-DG glycan and laminin. To evaluate the tumor formation in vivo, PC3-H and -L were inoculated in the orthotopic prostate of SCID mice. Because specific loss of β3-N-acetylglucosaminyltransferase-1 (β3GnT1) in PC3-L was identified, invasion and migration activity were analyzed in β3GnT1 transfected PC3-L cells. In PC3-H, β3GnT1 was inhibited by siRNA to evaluate the invasion activity, ERK/AKT phosphorylation and tumor formation in SCID mice. RESULTS In aggressive prostate carcinoma cell lines, laminin-binding glycans are dramatically decreased, although the amount of α-DG and β-dystroglycan is maintained. The decrease of laminin-binding glycans and consequent increased cell migration were associated with the decreased expression of β3GnT1. Forced expression of β3GnT1 in aggressive cancer cells restored the laminin-binding glycans and decreased tumor formation. SiRNA assays showed β3GnT1 plays a critical role in the synthesis of the laminin-binding glycans on α-DG by collaboration with LARGE genes. Interaction of the laminin-binding glycans with laminin and other adhesive molecules in BM attenuates tumor cell migratory potential by antagonizing ERK/AKT phosphorylation induced by the components in the ECM. CONCLUSIONS These findings suggest the key role of α-DG glycans and β3GnT1 in prostate cancer suppression. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e114 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Metrics Author Information Shingo Hatakeyama Hirosaki, Japan More articles by this author Xingfeng Bao La Jolla, CA More articles by this author Noriko Tokui Hirosaki, Japan More articles by this author Teppei Okamoto Hirosaki, Japan More articles by this author Kengo Imanishi Hirosaki, Japan More articles by this author Yusuke Ishibashi Hirosaki, Japan More articles by this author Hiromi Murasawa Hirosaki, Japan More articles by this author Yuichiro Suzuki Hirosaki, Japan More articles by this author Naoki Sugiyama Hirosaki, Japan More articles by this author Hayato Yamamoto Hirosaki, Japan More articles by this author Shigemasa Kudo Hirosaki, Japan More articles by this author Takahiro Yoneyama Hirosaki, Japan More articles by this author Takuya Koie Hirosaki, Japan More articles by this author Noritaka Kamimura Hirosaki, Japan More articles by this author Minoru Fukuda La Jolla, CA More articles by this author Chikara Ohyama Hirosaki, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...