New therapy for renal cell carcinoma with down regulation of glycosyltransferase gene

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591676
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Tohoku University
• Principal Investigator: ITO Akihiro Tohoku University Hospital, Research associate, 病院, 助手 (70344661)
• Co-Investigator(Kenkyū-buntansha): OGAWA Osamu Kyoto University, Faculty of medicine, Professor, 医学研究科, 教授 (90260611) ; KAMOTO Toshiyuki Kyoto University, Faculty of medicine, Associate professor, 医学研究科, 助教授 (00281098) ; NISHIYAMA Hiroyuki Kyoto University, Faculty of medicine, Research associate, 医学研究科, 助手 (20324642) ; SAITO Seiichi Tohoku University, Graduate School of medicine, associate professor, 大学院医学系研究科, 助教授 (80235043) ; ARAI Yoichi Tohoku University, Graduate School of medicine, Professor, 大学院医学系研究科, 教授 (50193058)
• Project Period (FY): 2005 – 2006
• Keywords: renal cell carcinoma / glycolipid / ganglioside / Siglec-7 / DSGb5 / St6GalNAcVI / siRNA / cell motility

Research Abstract

We have investigated changes of ganliosides in renal cell carcinoma (ROC) in regard to the malignant potential and found that the long chain gangliosides increased in metastasis, one of which is disialosyl globopentaosylceramide (DSGb5). The purpose of this project is to clarify the functional role of DSGb5. We have identified that 2,6-sialyltransferase (ST6GalNAcVI) catalyzes transfer of sialic acid to monosialosyl globopentaosylceramide (MSGb5) to synthesizes DSGb5. Down-regulation of ST6GalNAcVI mRNA by siRNA has led to decreases of motility of human renal cell carcinoma cells (ACHN cells) in vitro and decreases of cell growth of ACHN in nude mice. From these findings, DSGb5 has relevance to motility and growth of ACHN cells and down-regulation of ST6GalNac VI gene may become a new therapy for RCC.

Research Products

• [Journal Article] Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells : downregulation of ST6GalNAc VI in renal cancers. (2007)
  • Author(s): Senda M, Ito A, Tsuchida A, Hagiwara T, Kaneda T, Nakamura Y, Frukawa K
  • Journal Title: Biochem J. 402・3 Pages: 459-470
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells : downregulation of ST6GalNAc VI in renal cancers. (2007)
  • Author(s): Senda M, Ito A, Tsuchida A, Hagiwara T, Kaneda T, Nakamura Y, Frukawa K
  • Journal Title: Biochem J 402(3) Pages: 459-470
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 腎細胞癌の現状と治療戦略. (2006)
  • Author(s): 荒井陽一, 庵谷尚正, 伊藤明宏, 川村貞文, 佐藤信
  • Journal Title: Pharma Medica 24・11 Pages: 80-89
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Current state and treatment strategy of renal cell carcinoma (2006)
  • Author(s): Arai Y, Hiroya N, Ito A, Kawamura S, Sato M
  • Journal Title: Pharma Medica 24・11 Pages: 80-89
  • Description: 「研究成果報告書概要(欧文)」より