Identification of regulatory molecules related to the differentiation of glioma stem-like cells by an integrated protoemics.

• Project/Area Number: 24701007
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnosis
• Research Institution: Kumamoto University
• Principal Investigator: NAMBU AKIKO 熊本大学, 大学院生命科学研究部, 研究員 (40572087)
• Research Collaborator: ARAKI Norie 熊本大学, 大学院生命科学研究部, 准教授 (80253722) ; NAGAI Minako 熊本大学, 大学院生命科学研究部, 技術補佐員
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: がん幹細胞 / 分化 / 細胞外マトリックス / 接着分子 / 脳腫瘍 / プロテオミクス / DNAマイクロアレイ / 融合プロテオミクス / 分化ニッチ / プロテオーム / 分化誘導 / 細胞接着因子 / 腫瘍マーカー

Research Abstract

In this study, to clarify the molecular mechanism of GSC differentiation, we established GSC clones having the potential to differentiate into glioblastoma, and subjected to DNA microarray and iTRAQ based integrated proteomics. We combined all of the data obtained from the integrated proteomics by utilizing sequential data mining software. GO analysis revealed that the expression of cell adhesion molecules, including integrin aV, and extracellular matrices (ECMs), such as fibronectin 1, was significantly upregulated during serum-induced GSC differentiation. Combinational treatments with integrin inhibitors and anti-cancer drug temozolomide (TMZ) significantly suppressed early events in GSC differentiation, glioma progression and lead the longer survival of mouse GSC xenograft models. These results indicate that GSCs induce/secrete ECMs to develop microenvironments with serum factors, namely differentiation niches that further stimulate GSC differentiation and proliferation.

Research Products

• [Journal Article] Glioma initiating cells form a differentiation niche via the induction of extracellular matrices and integrinαV (2013)
  • Author(s): Akiko Niibori- Nambu, Midorikawa U, Mizuguchi S, Hide T, Nagai M, Komohara Y, Nagayama M, Hirayama M, Kobayashi D, Tsubota N, Takezaki T, Makino K, Nakamura H, Takeya M, Kuratsu K, Araki N
  • Journal Title: PLoS ONE Volume: 8(5)
  • Peer Reviewed
• [Journal Article] Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in NF1 disease model cells (2013)
  • Author(s): Hirayama M, Kobayashi D, Mizuguchi S, Morikawa T, Nagayama M, Midorikawa U, Wilson MM, Nambu Akiko Niibori, Yoshizawa AC, Kawano S, Araki N
  • Journal Title: Mol Cell Proteomics Volume: 12(5) Pages: 1377-94
  • Peer Reviewed
• [Journal Article] Epiplakin modifies the motility of the HeLa cells and accumulates at the outer surfaces of 3-D cell clusters (2013)
  • Author(s): Shimada H, Nambu- Niibori A , Wilson-Morifuji M, Mizuguchi S, Araki N, Sumiyoshi H, Sato M, Mezaki Y, Senoo H, Ishikawa K, Hatano Y, Okamoto O, Fujiwara S
  • Journal Title: J Deramatol Volume: 40(4) Pages: 249-58
  • Peer Reviewed
• [Journal Article] Glioma Initiating Cells Form a Differentiation Niche Via the Induction of Extracellular Matrices and Integrin aV (2013)
  • Author(s): Akiko Niibori-Nambu, Uichi Midorikawa, Souhei Mizuguchi, Takuichiro Hide, Minako Nagai,Yoshihiro Komohara, Megumi Nagayama, Mio Hirayama, Daiki Kobayashi, Nobuyuki Tsubota,Tatsuya Takezaki, Keishi Makino, Hideo Nakamura, Motohiro Takeya, Junichi Kuratsu, Norie Araki
  • Journal Title: PLoS ONE Volume: 8(5) Issue: 5 Pages: e59558-e59558
  • DOI: 10.1371/journal.pone.0059558
  • Peer Reviewed
• [Journal Article] Epiplakin modifies the motility of the HeLa cells and accumulates at the outer surfaces of 3-D cell clusters. (2013)
  • Author(s): Shimada H, Nambu-Niibori A, Wilson-Morifuji M, Mizuguchi S, Araki N, Sumiyoshi H, Sato M, Mezaki Y, Senoo H, Ishikawa K, Hatano Y, Okamoto O, Fujiwara S
  • Journal Title: J Dermatol Volume: 40 Issue: 4 Pages: 249-58
  • DOI: 10.1111/1346-8138.12076
  • Peer Reviewed
• [Journal Article] Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in NF1 disease model cells. (2013)
  • Author(s): Hirayama M, Kobayashi D, Mizuguchi S, Morikawa T, Nagayama M, Midorikawa U, Wilson MM, Nambu AN, Yoshizawa AC, Kawano S, Araki N.
  • Journal Title: Molecular & Cellular Proteomics Volume: 28 Issue: 5 Pages: 1377-94
  • DOI: 10.1074/mcp.m112.024802
  • Peer Reviewed
• [Journal Article] Contribution of RIZ1 to regulation of proliferation and migration of a liver fluke-related cholangiocartinoma cell (2012)
  • Author(s): Khaenam P, Niibori A , Okada S, Jearanaikoon P, Araki N, Limpaiboon T
  • Journal Title: Asian Pac J Cancer Prev Volume: 13 (8) Pages: 4007-11
  • Peer Reviewed
• [Presentation] Integrated Proteomics Identified the Differentiation Niche Induced by Glioma Stem Cells (2013)
  • Author(s): A. Niibori Nambu, U Midorikawa, S. Mizuguchi, T. Hide, M. Nagai, Y. Komohara, M. Nagayama, M. Hirayama, D. Kobayashi, H. Nakamura, M. Takeya, J. Kuratsu, N. Araki
  • Organizer: The Human Proteome Organization (HUPO) 12^<th> Annual World Congress
  • Place of Presentation: Pacifico Yokohama, Yokohama, Japan
• [Presentation] Integrated Proteomics Identified the Differentiation Niche Induced by Glioma Stem Cells (2013)
  • Author(s): A. Niibori Nambu
  • Organizer: The Human Proteome Organization (HUPO) 12th Annual World Congress
  • Place of Presentation: 神奈川県横浜市国際展示場
• [Book] 「神経線維腫症2型」母斑と母斑症皮膚科臨床アセット15 (2013)
  • Author(s): 荒木令江, 南部晶子, 小林大樹
• [Book] 神経線維腫症2型 (2013)
  • Author(s): 荒木令江, 南部晶子, 小林大樹
  • Total Pages: 384
  • Publisher: 中山書店