Proteomic analysis of membrane vesicles for elucidation of tumor communication mechanism and identification of tumor markers

• Project/Area Number: 25460715
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: Kume Hideaki 国立研究開発法人医薬基盤・健康・栄養研究所, プロテオームリサーチプロジェクト, 研究員 (50322714)
• Co-Investigator(Kenkyū-buntansha): TOMONAGA Takeshi 独立行政法人医薬基盤研究所, プロテオームリサーチプロジェクト, プロジェクトリーダー (80227644) ; MATSUBARA Hisahiro 千葉大学, 医学系研究科, 教授 (20282486)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌 / プロテオミクス / 細胞外小胞 / プロテオーム

Outline of Final Research Achievements

We have previously performed quantitative proteomic analysis of membrane fractions prepared from colorectal cancer tissues and benign polyps for biomarker discovery. In this study, we investigated whether the biomarker candidates could be detected in extracellular vesicle (EV) fraction prepared from serum samples. The EV fraction was prepared from serum samples of controls and colorectal cancer patients with or without metastasis by ultracentrifugation. A total of 20 proteins were quantitated by selected reaction monitoring (SRM) and three of them were shown to be increased in cancer patients with metastasis compared with controls or cancer patients without metastasis. In addition, these proteins were significantly elevated even in early stages compared with control in an independent set of patient samples. Accordingly, these proteins may be useful tumor markers for the diagnosis of colorectal cancer.

Research Products

• [Journal Article] Discovery of colorectal cancer biomarker candidates by membrane proteomic analysisand subsequent verification using selected reaction monitoring and tissue microarrayanalysis (2014)
  • Author(s): Kume H, Muraoka S, Kuga T, Adachi J, Narumi R, Watanabe S, Kuwano M, Kodera Y, Matsushita K, Fukuoka J, Masuda T, Ishihama Y, Matsubara H, Nomura F, Tomonaga T.
  • Journal Title: Mol Cell Proteomics. Volume: M113 Issue: 6 Pages: 37093-37093
  • DOI: 10.1074/mcp.m113.037093
  • Peer Reviewed
• [Journal Article] A novel mechanism of keratin cytoskeleton organization through casein kinase I alpha and FAM83H in colorectal cancer. (2013)
  • Author(s): Kuga, T., Kume, H., Kawasaki, N., Sato, M., Adachi, J., Shiromizu, T., Hoshino, I., Nishimori, T., Matsubara, H., and Tomonaga T.
  • Journal Title: J Cell Sci Volume: 126 Pages: 4721-31
  • DOI: 10.1242/jcs.129684
  • Peer Reviewed
• [Presentation] 血中細胞外小胞のプロテオーム解析による大腸癌バイオマーカーの探索 (2015)
  • Author(s): 久米秀明、星野敢、松原久弘、朝長毅
  • Organizer: 第74回日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] 血中細胞外小胞のプロテオーム解析による大腸癌バイオマーカーの探索 (2015)
  • Author(s): 久米秀明、星野敢、松原久弘、朝長毅
  • Organizer: 第35回日本分子腫瘍マーカー研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-07
• [Presentation] SRM/MRM法を用いた血中細胞外小胞画分における大腸癌バイオマーカー候補タンパク質の検証 (2015)
  • Author(s): 久米秀明、小松亜紀、星野敢、松原久弘、朝長毅
  • Organizer: 第11回日本プロテオーム学会
  • Place of Presentation: 熊本
  • Year and Date: 2015-07-23
• [Presentation] 血中膜小胞画分のプロテオーム解析による大腸癌バイオマーカーの探索 (2014)
  • Author(s): 久米秀明、橋本裕希、村岡賢、松原久裕、朝長毅
  • Organizer: 第1回日本細胞外小胞学会
  • Place of Presentation: 広島
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] 血中膜小胞画分のプロテオーム解析による大腸癌バイオマーカータンパク質の探索 (2014)
  • Author(s): 久米秀明、橋本裕希、村岡賢、松原久裕、朝長毅
  • Organizer: 第12回日本プロテオーム学会
  • Place of Presentation: 筑波
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] 大腸癌組織膜タンパク質のプロテオーム解析によるバイオマーカー探索とSRM/MRM法を用いたその検証 (2014)
  • Author(s): 久米秀明、村岡賢、久家貴寿、足立淳、小寺義男、石濱泰、松原久裕、朝長毅
  • Organizer: 第62回質量分析総合討論会
  • Place of Presentation: 吹田
  • Year and Date: 2014-05-14 – 2014-05-16
• [Presentation] Discovery and subsequent validation of biomarkers for colorectal cancer by large-scale proteomic analysis and tissue microarray analysis (2013)
  • Author(s): Kume H, Muraoka S, Hashimoto Y, Watanabe S, Masuda T, Ishihama Y, Fukuoka J, Kodera Y, Matsushita K, Matsubara H, Tomonaga T
  • Organizer: Human Proteome Organization (HUPO) 12th Annual World Congress
  • Place of Presentation: Yokohama