Reverse Glycomic Approach for Development of Simple Diagnostic Method of Antitumor-Drug Resistance

• Project/Area Number: 23770120
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Hiroshima University
• Principal Investigator: NAKANO Miyako 広島大学, 先端物質科学研究科, 准教授 (40397724)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: 糖質 / 糖鎖 / 癌 / 構造解析 / 薬物耐性 / 白血病 / 微小管脱重合阻害薬

Research Abstract

To develop simple diagnostic method of antitumor-drug resistance, we determined the changes in glycosylation that occur on membrane proteins of drug-resistant T-cell acute lymphoblastic leukemia cell line. Drug-resistant cells showed a significant decrease in sialylated glycans. To ascertain if identical alterations occurred on leukemia cell in the blood of leukemia patients, the analytical conditions for LC-ESI MS of glycan structures were investigated. We established the conditions that could analyze their glycan structures using 3 mL of blood. Moreover, we showed that the lectin recognized sialic acids was useful for investigating a simple diagnostic method of drug-resistance acquisition.

Research Products

• [Journal Article] Identification of glycan structure alterations on cell membrane proteins in desoxyepothilone B resistant leukemia cells (2011)
  • Author(s): Nakano M, Saldanha R, Gobel A, Kavallaris M, Packer N
  • Journal Title: Molecular & Cellular Proteomics Volume: 10 (11) Issue: 11 Pages: M111.009001-M111.009001
  • DOI: 10.1074/mcp.m111.009001
  • NAID: 120006782319
  • Peer Reviewed
• [Presentation] Alterations of glycan structures on cell membrane glycoproteins in microtubule-targeting drug-resistant leukemia cells (2012)
  • Author(s): Nakano M, Shirai R, Ito J, Takahashi S
  • Organizer: 31stJapanese Carbohydrate Symposium
  • Place of Presentation: Kagoshima, Japan
• [Presentation] Identification of alterations in glycan structure on cell membrane proteins in microtubule-targeting drug-resistant leukemia cells (2012)
  • Author(s): NakanoM, TaniguchiN, Ito J, ShiraiR, KavallarisM, Packer
  • Organizer: Human Proteome Organization 11thAnnual World Congress
  • Place of Presentation: Boston, MA, U.S.A
• [Presentation] 微小管作用抗癌剤の耐性獲得による白血病細胞膜糖タンパク質糖鎖の構造変化 (2012)
  • Author(s): 中の三弥子、白井亮平、伊藤潤、高橋志郎
  • Organizer: 第31回 日本糖質学会年会
  • Place of Presentation: 鹿児島
• [Presentation] Identification of alterations in glycan structure on cell membrane proteins in microtubule-targeting drug-resistant leukemia cells (2012)
  • Author(s): Nakano M, Taniguchi N, Ito J, Shirai R, Kavallaris M, Packer N
  • Organizer: Human Proteome Organization 11th Annual World Congress
  • Place of Presentation: Boston, MA, U.S.A.
• [Presentation] Site-specific analyses of N-glycans on haptoglobin in sera of patients with various kinds of gastroenterological cancers (2012)
  • Author(s): Takahashi S, Amimoto T, Kawamoto S, Ono K, Miyoshi E, Nakano M
  • Organizer: Human Proteome Organization 11th Annual World Congress
  • Place of Presentation: Boston, MA, U.S.A.
• [Presentation] Drug-resistance inhibits expression of alpha2-6 sialylation on cell membrane glycoproteins (2011)
  • Author(s): Nakano M, Ota F, Nakajima K, Taniguchi N, Kavallaris M, Packer N
  • Organizer: 21stInternational Symposium glycoconjugates
  • Place of Presentation: Vienna, Austria
• [Presentation] Drug-resistance inhibits expression of alpha2-6 sialylation on cell membrane glycoproteins (2011)
  • Author(s): Nakano M, Ota F, Nakajima K, Taniguchi N, Kavallaris M, Packer N
  • Organizer: 21st International Symposium glycoconjugates
  • Place of Presentation: Vienna, Austria