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Analysis of the origin of glioma cells, which focused on the relations to neural stem cells

Research Project

Project/Area Number 12557121
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Cerebral neurosurgery
Research InstitutionHyogo College of Medicine

Principal Investigator

ARITA Norio  Hyogo College of Medicine, Neurosurgery, Professor, 医学部, 教授 (80159508)

Co-Investigator(Kenkyū-buntansha) IKEMOTO Hideyasu  Hyogo College of Medicine, Neurosurgery, Research Associate, 医学部, 助手 (30278824)
NAKANO Atsuhisa  Hyogo College of Medicine, Neurosurgery, Research Associate, 医学部, 助手 (70258151)
TAMURA Kazuyoshi  Hyogo College of Medicine, Neurosurgery, Assistant Professor, 医学部, 講師 (40340971)
OKANO Hideyuki  Keio University School of Medicine, Physiology, Professor, 医学部, 教授 (60160694)
松本 強  兵庫医科大学, 医学部, 講師 (00181777)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥8,100,000 (Direct Cost: ¥8,100,000)
Keywordsneural stem cell / glioblastoma / oligodendroglioma / oligoastrocytoma / ependymoma / medulloblastoma / Musashi1 / GFAP / glioma / ependvmoma / Nestin / Musashi 1 / ependymoma / cell culture / Hu / MSI1 / NG2 / PDGF-αR
Research Abstract

The origin of glioma is still controversial. Neural stem cells or neural progenitor cells might develop to glioma cells. To investigate the origin of gliomas, we examined the expression of the human Musashi1 homologue (MSI1) and nestin in human glioma tissues and cultured glioma cells. In glioblastomas, MSI1 was expressed in GFAP-negative tumor cells forming foci that were clearly demarcated and surrounded by GEAP-positive cells. Tumor cells arranged in pseudopalisades were also strongly immunoreactive with MSI1 antibodies. These tumor cells are assumed to be actively proliferating, and to have the character of neural stem cells.
Oligoastrocytomas expressed MSI1 and some of them could express Hu (immature neuronal cell marker). Oligoastrocytomas are thought to be derived from more immature and multipotent cells compared with oligodendrogliomas, which could express GFAP, but not MSI1.
Recent study revealed that ependymal cells seem to be the multipotent neural stem cells. Ependymoma ceils … More might show the similar characters like their precursor cells. The origin of medulloblastoma cell has been thought as an immature progenitor *** that can give rise to either neuronal or glial cells. We characterized both ependymoma and medulloblastoma cells to investigate their potential ability of differentiation. Ependymoma cells expressed Musashi1, nestin, A2B5 and did not express Tuj1 and Synaptophysin. Long-term cultured ependymoma cells expressed Tuj1 and Synaptophysin. Medulloblastoma cells expressed Musashi1, Nestin, A2B5 and did not express GFAP. Medulloblastoma cells treated with LIF (leukemia inhibitory factor) and BMP-2 (bone morphogenetic protein-2) could also express GFAP, according to the in vitro conditions that neural stem cells could differentiate to astrocytes. Our study suggested that ependymoma cells might be able to differentiate into neural cells and medulloblastoma cells might be able to differentiate into glial cells.
These results may support the hypothesis that glioma cells are derived from multipotent neural stem cells. Less

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Velasco G, Nakano. A, et al.: "MT6-matrix metalloproteinase : identification, progelatinase A activation, and expression in brain tumors"Cancer Res. 60. 872-877 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikemoto H, Arita N, et al.: "Calphostin C-mediated translocation of Bax into mitochondria induces cytochroirie c release before mitochondrial dysfunction"Cell Death Differ. 7. 511-520 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanemura Y, Nakano A.Tamura K., Okano H., Arita N., et al.: "Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity"Differentiation. 68. 141-152 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura K., et al.: "Eradication of murine brain tumors by direct inoculation of concentrated high titerrecombinant retrovirus harboring herpes simplex virus thymidine kinase gene"Gene Ther. 8. 215-222 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanemura Y., Arita N., Okano H., et al.: "Evaluation of in vitro proliferative activity of human fetal neural stem/progenitor cells using indirect measurements of viable cells based on cellular metabolic activity"J Neurosci Res. 69. 869-879 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori K., Nakano A., Ikemoto H., Arita N., et al.: "Brain-specific angiogenesis inhibitor 1 (BAI1) is expressed in human cerebral neuronal cells"Neurosci Res. 43. 69-74 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 有田憲生他(高倉公明監修): "グリオーマの治療-ポストゲノム時代への展望-脳神経外科の最先端No.2"先端医療技術研究所. 8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takagi M, Arita N, et al.: "Estrogen deficiency is a potential cause for osteopenia in adult male patients with Noonan's syndrome"Calcif Tssue Int. 66. 200-203 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kasayama S, Arita N, et al.: "Impaired β-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients"Clin Endocrinol (Oxf). 52. 549-555 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohnishi T, Arita N, et al.: "Intracavemous sinus ectopic adrenocorticotropin-secreting tumours causing therapeutic failure in transsphenoidal surgery for Cushing's disease"Acta Neurochir (Wien). 142. 855-864 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuratsu J, Arita N, et al.: "Phase II trial of pre-irradiation KRN8602(MX2) in malignant glioma patients"J Neurooncol. 48. 145-149 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Velasco G, Nakano A, et al.: "MT6-matrix metalloproteinase : identification, progelatinase A activation, and expression in brain tumors"Cancer Res. 60. 872-877 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikemoto H, Arita N, et al.: "Calphostin C-mediated translocation of Bax into mitochondria induces cytochrome c release before mitochondrial dysfunction"Cell Death Differ. 7. 511-520 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Otsuki M, Arita N, et al.: "Characterization of premature atherosclerosis of carotid arteries in acromegalic patients"Clin Endocrinol. 54. 791-796 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanemura Y, Nakano A, Tamura K, Okano H, and Arita N, et al.: "Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity"Differentiation. 68. 141-152 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura K, et al.: "Eradication of murine brain tumors by direct inoculation of concentrated high titer-recombinant retrovirus harboring herpes simplex virus thymidine kinase gene"Gene Ther. 8. 215-222 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikenaka K, Tamura K, et al.: "Treatment of glioblastoma by direct inoculation of concentrated high titer-recombinant retrovirus carrying the herpes simplex virus thymidine kinase gene"Hum Cell. 14. 49-58 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanemura Y, Arita N, Okano H, et al.: "Evaluation of in vitro proliferative activity of human fetal neural stem/progenitor cells using indirect measurements of viable cells based on cellular metabolic activity"J Neurosci Res. 69. 869-879 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori K, Nakano A, Ikemoto H, Tamura K, Arita N, et al.: "Brain-specific angiogenesis inhibitor 1 (BAI1) is expressed in human cerebral neuronal cells"Neurosci Res. 43. 69-74 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Velasco G, Nakano A, et al.: "Human MT6-matrix metalloproteinase : identification, progelatinase A activation, and expression in brain tumors"Cancer Res. 60. 877-882 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanemura Y, Nakano A, Tamura K, Okano H, Arita N, et al.: "Musashi1, an evolutionarily conserved neural RNA-bining protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity"Differentiation. 68. 141-152 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikenaka K, Tamura K, et al.: "Treatment of glioblastoma by direct inoculation of concentrated high titer-recombinant retrovirus carrying the herpes simplex virus thymidine kinase gene"Hum Cell. 14. 49-58 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamura K, et al.: "Eradication of murine brain tumors by direct inoculation of concentrated high titer-recombinant retrovirus harboring herpes simplex virus thymidine kinase gene"Gene Ther. 8. 215-222 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori K, Nakano A, Ikemoto H, Tamura K, Arira N, et al.: "Brain-specific angiogenesis inhibitor 1 (BAI1) is expressed in human cerebral neuronal cells"Neurosci Res. 43. 69-74 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanemura Y, Arita N, et al.: "Evaluation of in vitro proliferative activity of human fetal neural stem/progenitor cells using indirect measurements of viable cells based on cellular metabolic activity"J Neurosci Res. 69. 869-879 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Velasco G, Nakano A, et al.: "Human MT6-matrix metalloproteinase : identification, progelatinase A activation, and expression in brain tumors"Cancer Res.. 60. 877-882 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanemura Y, Nakano A, Tamura K, Okano H, Arita N, et al.: "Musashil, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity"Differentiation. 68. 141-152 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Otsuki M, Arita N, et al.: "Characterization of premature atherosclerosis of carotid arteries in acromegalic patients"Clin. Endocrinol. 54. 791-796 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tamura K, et al.: "Eradication of murine brain tumors by direct inoculation of concentrated high titer-recombinant retrovirus harboring herpes simplex virus thymidine kinase gene"Gene Ther. 8. 215-222 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikenaka K, Tamura K, et al.: "Treatment of glioblastoma by direct inoculation of concentrated high titer-recombinan retrovirus carrying the herpes simplex virus thymidine kinase gene"Hum. Cell. 14. 49-58 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mori K, Nakano A, Ikemoto H, Tamura K, Arita N, et al.: "Brain-specific angiogenesis inhibitor 1 (BAI 1) is expressed in human cerebral neuronal cells"Neuroscience Research. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikemoto H,Arita N, et al: "Calphostin C-mediated translocation and integration of Bax into mitochondria induces cytochrome c release before mitochondrial dysfunction."Cell Death Differ. 7. 511-520 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kasayama S,Arita N, et al: "Impaired β-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients."Clin Endocrinol. 52. 549-555 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kuratsu J,Arita N, et al: "Phase II trial of pre-irradiation KRN8602(MX2) in malignant glioma patients."J Neuro-Oncol. 48. 145-149 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Velasco G,Nakano A, et al: "Human MT6-matrix metalloproteinase : indentification, progelatinase A activation, and expression in brain tumors."Cancer Res. 60. 877-882 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawaguchi A,Okano H, et al: "Nestin-EGFP transgenic mice : Visualization of the self-renewal and multipotency of CNS stem cells."Mol Cell Neurosci. 17. 259-273 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaneko Y,Okano H, et al: "Musashi 1 : an evolutionally conserved marker for CNS progenitor cells including neural stem cells."Dev Neurosci. 22. 139-153 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 有田憲生: "脳神経外科の最先端No.2、21世紀の新領域とニューテクノロジー"先端医療技術研究所. 8 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2025-11-20  

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