Possiblity of fatty acid binding protein as a diagnostic and therapeutic target in glioma

• Project/Area Number: 25670274
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Yamaguchi University
• Principal Investigator: OWADA Yuji 山口大学, 医学(系)研究科(研究院), 教授 (20292211)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Michiyasu 山口大学, 大学院医学系研究科, 教授 (80196873)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: FABP / 脳腫瘍 / 診断マーカー / 増殖 / 膠芽腫 / ELISA / 脂肪酸結合蛋白質 / グリオーマ / 幹細胞

Outline of Final Research Achievements

In this study, we tried to develop the sensitive diagnostic tool for glioblastoma focusing on fatty acid binding protein (FABP7), and examined the possibility as a regulator of glioma proliferation. We firstly established the sensitive ELISA assay system to detect FABP7 and measured its concentration in the cerebro-spinal fluid (CSF) samples from the patient suffering from glioma. As a result, FABP7 concentration in the CSF was markedly elevated in the glioblastoma patients compared with healthy controls. In the pathological examination in glioma samples, levels of FABP7 expression were significantly correlated with their malignancy grade. Furthermore, suppression of FABP7 expression in glioma stem cell lines by siRNA transfection resulted in the decreased proliferation.

Research Products

• [Journal Article] Proteomic differential display analysis reveals decreased expression of PEA-15 and vimentin in FABP7-deficient astrocytes. (2015)
  • Author(s): Ebrahimi, M., Sharifi, K., Islam, A., Miyazaki, H., Yasumoto, Y., Kagawa, Y., Yamamoto, Y., Kitagawa, T., Kuramitsu, Y., Nakamura, K. and Owada, Y.
  • Journal Title: J Proteom Bioinform Volume: 8 Pages: 9-14
  • Peer Reviewed / Open Access
• [Journal Article] Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin-1. (2015)
  • Author(s): Yoshiteru Kagawa, Yuki Yasumoto, Kazem Sharifi, Majid Ebrahimi, Ariful Islam, Hirofumi Miyazaki, Yui Yamamoto, Tomoo Sawada, Hiroko Kishi, Sei Kobayashi, Motoko Maekawa, Takeo Yoshikawa, Eiichi Takaki, Akira Nakai, Hiroshi Kogo, Toyoshi Fujimoto and Yuji Owada
  • Journal Title: Glia Volume: 63 Issue: 5 Pages: 780-794
  • DOI: 10.1002/glia.22784
  • Peer Reviewed / Open Access
• [Journal Article] Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans. (2014)
  • Author(s): Nomura, S., Fujii, M., Inoue, T., He, Y., Maruta, Y., Koizumi, H., Suehiro, E., Imoto, H., Ishihara, H., Oka, F., Matsumoto, M.,Owada, Y., Yamakawa, T. and Suzuki, M.
  • Journal Title: Epilepsia. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Preservation of cochlear function in Fabp3 (H-Fabp) knockout mice. (2014)
  • Author(s): Suzuki, J., Oshima, T., Yoshida, N., Kimura, R., Takata, Y., Owada, Y., Kobayashi, T. and Osumi, N.
  • Journal Title: Neurosci Res. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Spinal cord ischemia/injury. (2014)
  • Author(s): Ishikawa, T., Suzuki, H., Ishikawa, K., Yasuda, S., Matsui, T., Yamamoto, M., Kakeda, T., Yamamoto, S., Owada, Y. and Yaksh, TL.
  • Journal Title: Curr Pharm Design. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Hyperlocomotor activity and stress vulnerability during adulthood induced by social isolation after early weaning are prevented by voluntary running exercise before normal weaning period. (2014)
  • Author(s): Ishikawa, J., Ogawa, Y., Owada, Y. and Ishikawa A.
  • Journal Title: Behavior Brain Res Volume: in press Pages: 197-206
  • DOI: 10.1016/j.bbr.2014.02.007
  • Peer Reviewed
• [Journal Article] nvolvement of bone marrow-derived vascular progenitor cells in neovascularization during follicular development in mice. (2014)
  • Author(s): Kizuka-Shibuya, F., Tokuda, N., Takagi, K., Adachi, Y., Lee, L., Tamura, I., Maekawa, R., Tamura, H., Suzuki, T., Owada, Y. and Sugino N.
  • Journal Title: J Ovarian Res Volume: 7 Issue: 1 Pages: 10-10
  • DOI: 10.1186/1757-2215-7-10
  • Peer Reviewed
• [Journal Article] Pathological features of highly invasive glioma stem cells in a mouse xenograft model. (2013)
  • Author(s): Sadahiro, H., Yoshikawa, K., Ideguchi, M., Kajiwara, K., Ishii, A., Ikeda, E., Owada, Y., Yasumoto, Y. and Suzuki, M.
  • Journal Title: Brain Tumor Pathol Volume: 31 Issue: 2 Pages: 77-84
  • DOI: 10.1007/s10014-013-0149-x
  • Peer Reviewed
• [Journal Article] Fatty acid binding protein 7 as a marker for glioma stem cells. (2013)
  • Author(s): Morihiro, Y., Yasumoto, Y., Koshy, VL., Sadahiro, H., Uchida, T., Inamura, A., Sharifi, K., Ideguchi, M., Nomura, S., Tokuda, N., Kashiwabara, S., Ishii, A., Ikeda, E., Owada , Y. * and Suzuki, M. (* corresp. author)
  • Journal Title: Pathol Int Volume: 63 Issue: 11 Pages: 546-553
  • DOI: 10.1111/pin.12109
  • Peer Reviewed
• [Journal Article] Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells (2013)
  • Author(s): Sharifi K, Yoshikawa
  • Journal Title: Cell and Tissue Research Volume: 354 Issue: 3 Pages: 683-695
  • DOI: 10.1007/s00441-013-1730-7
  • Peer Reviewed
• [Journal Article] The effect of hypothermia therapy in neonatal mice on the cortical laminar disruption following ischemic injury in neonatal mice. (2013)
  • Author(s): Kida, H., Nomura, S., Shinoyama, M., Ideguchi, M., Owada, Y. and Suzuki, M.
  • Journal Title: PLos One Volume: 8 Issue: 7 Pages: e68877-e68877
  • DOI: 10.1371/journal.pone.0068877
  • Peer Reviewed
• [Journal Article] Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5. (2013)
  • Author(s): Inamura, A., Adachi, Y., Inoue, T., He, Y., Tokuda, N., Nawata, T., Shirao, S., Nomura, S., Fujii, M., Ikeda, E., Owada, Y. * and Suzuki, M. (* corresp. author)
  • Journal Title: Neurochem Res Volume: 38 Issue: 8 Pages: 1641-1647
  • DOI: 10.1007/s11064-013-1066-4
  • Peer Reviewed
• [Presentation] グリオーマ幹細胞における脂肪酸結合タンパク質（FABP7）および脂肪酸合成酵素（FASN）の発現と機能 (2014)
  • Author(s): 安本有希、大和田祐二
  • Organizer: 第2回がんと代謝研究会
  • Place of Presentation: 東京理科大学図書館大ホール（東京都葛飾区）
  • Year and Date: 2014-07-10
• [Presentation] FABP7 is involved in epigenetic modification in astrocytes.
  • Author(s): Kagawa, Y.
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] Fatty acid binding protein 3 (FABP3) regulates cognitive function and anxiety behaviors.
  • Author(s): Yamamoto, Y.
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego(USA)
• [Presentation] FABP7-deficiency altered membrane lipid raft formation in astrocytes.
  • Author(s): Kagawa, Y.
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego(USA)
• [Presentation] Fatty acid-binding protein 7 (FABP7) regulates lipid raft formation in astrocytes.
  • Author(s): Kagawa, Y.
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] 脂肪酸結合タンパク質FABP3欠損マウスにおける認知機能及び情動行動異常の神経機序
  • Author(s): 山本由似
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 国立京都国際会館（京都）
• [Remarks] 山口大学大学院医学系研究科 器官解剖学分野研究室HP
  • URL: http://ds.cc.yamaguchi-u.ac.jp/~org-anat/
• [Patent(Industrial Property Rights)] 難聴が生じにくいモデル動物 (2013)
  • Inventor(s): 鈴木淳、大隅典 子、高田雄介、大 和田祐二
  • Industrial Property Rights Holder: 東北大学・山口大 学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-09-13
  • Overseas