MP21-08 GLYCAN MODIFICATION OF PODOPLANIN ENHANCES GROWTH FACTOR PRODUCTION THROUGH STABILIZATION OF PLATELET AGGREGATION IN BLADDER CANCER CELL

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2014MP21-08 GLYCAN MODIFICATION OF PODOPLANIN ENHANCES GROWTH FACTOR PRODUCTION THROUGH STABILIZATION OF PLATELET AGGREGATION IN BLADDER CANCER CELL Yuki Tobisawa, Shingo Hatakeyama, Tohru Yoneyama, Teppei Okamoto, Hayato Yamamoto, Kazuyuki Mori, Akiko Okamoto, Atsushi Imai, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, and Chikara Ohyama Yuki TobisawaYuki Tobisawa More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Tohru YoneyamaTohru Yoneyama More articles by this author , Teppei OkamotoTeppei Okamoto More articles by this author , Hayato YamamotoHayato Yamamoto More articles by this author , Kazuyuki MoriKazuyuki Mori More articles by this author , Akiko OkamotoAkiko Okamoto More articles by this author , Atsushi ImaiAtsushi Imai More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Takuya KoieTakuya Koie More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.836AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Platelet aggregation together with cancer cell is one of the key factors for cancer progression and metastasis. Podoplanin (PDPN), which is known as a lymphatic endothelial marker, expressed on cancer cell surface has a potential of platelet aggregation through interaction with CLEC-2 expressed on Platelet. Core2 β-1,6-N-acetylglucosaminyltransferase (C2GnT) is a key enzyme for O-glycosylation of membrane proteins. Although PDPN has a core2 O-glycosylation site on their mucin domain, its roll in cancer progression is still unclear. Here, we examine the roles of PDPN and their O-glycosylation in bladder cancer (BCa) progression and invasion. METHODS YTS-1 is a BCa cell line established from muscle invasive BCa and highly positive for PDPN and C2GnT. KK-47 is a BCa cell line established from non-muscle invasive BCa and expresses a faint level of PDPN and C2GnT. YTS-1 cells were transfected with PDPN-siRNA or C2GnT-siRNA to silence of PDPN or C2GnT expression. KK47 cells were transfected with pcDNA3.1-PDPN and/or pcDNA3.1-C2GnT to make KK47-PDPN, KK47-C2GnT and KK47-C2PDPN which are highly positive for PDPN, C2GnT or both of them. These cells were subjected to growth factor assays and invasion assay. Co-culture system of BCa cells and platelet was used to evaluate growth kinetics of the BCa cells and production of growth factors. In vitro invasion assay was used to evaluate invasion potential of the BCa cells. RESULTS In the co-culture system of BCa cells and platelet, BCa cells culturing with platelet had higher growth activity than without platelet (p<0.05). YTS-1 produced significantly higher amounts of bFGF, EGF, NGF beta, PDGF-BB, TGF-beta and VEGF when they are co-cultured with platelet than they are cultured without platelet (p<0.05). O-glycosylation of PDPN on BCa cells significantly increased the production of growth factors (p<0.05). When PDPN is knocked-down, invasive potential of YTS-1 was markedly reduced. (p=0.005). CONCLUSIONS These results suggest that expression of PDPN and its O-glycosylation enhance growth factors production, proliferation activity, and invasion potential of bladder cancer cells through interaction with platelet. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e228 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yuki Tobisawa More articles by this author Shingo Hatakeyama More articles by this author Tohru Yoneyama More articles by this author Teppei Okamoto More articles by this author Hayato Yamamoto More articles by this author Kazuyuki Mori More articles by this author Akiko Okamoto More articles by this author Atsushi Imai More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto More articles by this author Takuya Koie More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...