Characterization of the glycosylation pattern in cholangiolocellular carcinoma

• Project/Area Number: 15K19049
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: University of Fukui
• Principal Investigator: Hoshino Hitomi 福井大学, 学術研究院医学系部門, 特命助教 (90500710)
• Research Collaborator: KOBAYASHI Motohiro 福井大学, 学術研究院医学系部門, 教授 (00362137)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 細胆管細胞癌 / 糖鎖 / MUC1 / EMA

Outline of Final Research Achievements

This study was undertaken to determine whether sulfated glycans could serve as a cholangiolocellular carcinoma (CoCC) marker. We showed that sulfated glycans are preferentially expressed at the apical membrane of cholangiocytes found in small-sized intrahepatic bile ducts in normal liver and in canalicular structures formed in CoCC. We also reported that apical membrane expression of sulfated glycans colocalized with that of mucin 1 (MUC1) core proteins in CoCC. We showed that N-acetylglucosamine-6-O-sulfotransferase 2 (GlcNAc6ST-2) catalyze biosynthesis of sulfated glycans in cholangiocytes. These results indicate that apical membrane localization of MUC1 proteins decorated with GlcNAc6ST-2-dependent sulfated glycans may mark cholangiocytes with cholangiolar/ductular differentiation and could serve as a useful CoCC marker.

Research Products

• [Journal Article] Appearance of high endothelial venule-like vessels in benign prostatic hyperplasia is associated with lower urinary tract symptom (2017)
  • Author(s): Inamura S, Shinagawa T, Hoshino H, Sakai Y, Imamura Y, Yokoyama O, Kobayashi M
  • Journal Title: Prostate Volume: 77 Issue: 7 Pages: 794-802
  • DOI: 10.1002/pros.23319
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Apical membrane expression of distinct sulfated glycans represents a novel marker of cholangiolocellular carcinoma (2016)
  • Author(s): Hoshino H, Ohta M, Ito M, Uchimura K, Sakai Y, Uehara T, Low S, Fukushima M, Kobayashi M
  • Journal Title: Lab Invest Volume: 96 Issue: 12 Pages: 1246-1255
  • DOI: 10.1038/labinvest.2016.104
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] High endothelial venule-like vessels and lymphocyte recruitment in diffuse sclerosing variant of papillary thyroid carcinoma. (2016)
  • Author(s): Shulin L, Sakai Y., Hoshino H, Hirokawa M, Kawashima H, Higuchi K, Imamura Y, Kobayashi M
  • Journal Title: Pathology Volume: 48 Issue: 7 Pages: 666-674
  • DOI: 10.1016/j.pathol.2016.08.002
  • Peer Reviewed
• [Journal Article] A potential role for 6-sulfo sialyl Lewis X in metastasis of bladder urothelial carcinoma (2015)
  • Author(s): Taga M, Hoshino H, Low S, Imamura Y, Ito H, Yokoyama O, Kobayashi M
  • Journal Title: Urol Oncol Volume: 33 Issue: 11 Pages: 496.e1-496.e9
  • DOI: 10.1016/j.urolonc.2015.05.026
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Apical membrane expression of distinct sulfated glycans represents a novel marker of cholangiolocellular carcinoma (2017)
  • Author(s): Hoshino H, Ohta M, Ito M, Uchimura K, Sakai Y, Uehara T, Low S, Fukushima M, Kobayashi M
  • Organizer: 20th Annual San Diego Glycobiology Symposium
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2017-02-03
  • Int'l Joint Research
• [Presentation] High endothelial venule-like vessels and lymphocyte recruitment in diffuse sclerosing variant of papillary thyroid carcinoma (2017)
  • Author(s): Low S, Kanamori R, Sakai Y, Hoshino H, Hirokawa M, Kawashima H, Higuchi K, Imamura Y, Kobayashi M
  • Organizer: 20th Annual San Diego Glycobiology Symposium
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2017-02-03
  • Int'l Joint Research
• [Presentation] Apical membrane expression of distinct sulfated glycans represents a novel marker of cholangiolocellular carcinoma (2016)
  • Author(s): Hoshino H, Ohta M, Ito M, Uchimura K, Sakai Y, Uehara T, Low S, Fukushima M, Kobayashi M
  • Organizer: 26th Annual conference of the society for Glycobiology
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2016-11-19
  • Int'l Joint Research
• [Presentation] A potential role for 6-sulfo sialyl Lewis X in metastasis of bladder urothelial carcinoma (2016)
  • Author(s): Taga M, Hoshino H, Los S, Imamura Y, Ito H, Kobayashi M, Yokoyama O
  • Organizer: American Urology Association Annual Meeting
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] 膀胱癌に発現する硫酸化シアリルルイスXに関する検討 (2016)
  • Author(s): 多賀 峰克, 伊藤 英明, 品川 友親, 堤内 真美, 星野 瞳, 小林 基弘, 横山 修
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-04-23
• [Presentation] A potential role for 6-sulfo sialyl Lewis X in metastasis of bladder urothelial carcinoma (2015)
  • Author(s): Minekatsu Taga, Hitomi Hoshino, Shulin Low, and Motohiro Kobayashi
  • Organizer: Annual conference of the society for Glycobiology
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2015-12-01
  • Int'l Joint Research