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Analysis of the molecular mechanism of glioma invasion by using a brain slice invasion model

Research Project

Project/Area Number 10671297
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOsaka University

Principal Investigator

OHNISHI Takanori  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70233210)

Co-Investigator(Kenkyū-buntansha) IZUMOTO Shuichi  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手
平賀 章壽  大阪大学, 医学部, 助手 (40243232)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000)
Keywordsmalignant glioma / invasion model / tumor invasion / brain slice / matrix metalloproteinase / confocal laser scanning microscopy
Research Abstract

In order to quantitatively analyze the spatial extent of glioma cell migration in an organotypic brain slice culture, we developed a new invasion model with the aid of confocal laser scanning microscopy (CLSM). CLSM allowed not only for three-dimensional visualization of the invasive pattern of human T98G glioma cells in the living brain slice but also for serial analysis of the invasive process over several weeks. Twenty-four hours after the T98G glioma spheroid was initiated to coculture with a brain slice, the glioma cells detached themselves from the spheroid and spontaneously continued to migrate on the surface of the brain slice, while they diffusely invaded into the slice by migrating to a deeper site. Immunohistochemical analysis revealed that these migrating glioma cells much more strongly immunostained for matrix metalloproteinase (MMP)-2 and -9 than the tumor spheroid which remained at the implanted site. Treatment of the T98G glioma spheroid with 1, 10-phenanthroline, a specific inhibitor of MMPs, significantly inhibited not only the cell migration on the surface of the brain slice but also the invasion of the glioma cells into the slice. The present version of the glioma invasion model using CLSM makes it possible to spatially and serially analyze the extent of glioma cell invasion in the living brain slice for several weeks, making it a very useful tool for investigating the cellular and molecular mechanisms of glioma invasion under conditions most analogous to those of normal brains in vivo.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] T. Ohnishi: "Quantitative analysis of glioma cell invasion by confocal laser scanning microscopy in a novel brain slice model"Biochem Biophys Res Commun. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Kanemura: "Isolation and expression analysis of a novel human homologue of the Drosophia glial cells missing (gcm) gene"FEBS Lett.. 442. 151-156 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Ohnishi: "Role of fibronectin-stimulated tumor cell migration in glioma invasion in vivo : clinical significance of fibronectin and fibronectin receptor expressed in human glioma tissues"Clin Exp. Metastasis. 16. 729-741 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Ohnishi: "A novel model of glioma cell invasion using organotypic brain slice culture"Cancer Res. 58. 2935-2940 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Ohnishi: "In vitro and in vivo potentiation of radiosensitivity of malignant gliomas by antisense inhibition of the RAD51 gene"Biochem Biophys Res Commun. 245. 319-324 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Hiraga: "Telomerase activity and alterations in telomere length in human brain tumors"Cancer Res. 58. 2117-2125 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 大西 丘倫: "免疫学からみた神経系と神経疾患"日本医学館(東京). 374 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Ohnishi, et al: "Quantitative analysis of glioma cell invasion by confocal laser scanning microscopy in a novel brain slice model"Biochem Biophys Res Commun. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Kanemura, et al: "Isolation and expression analysis of a novel human homologue of the Drosophia glial cells missing(gcm)gene"FEBS Lett. 442. 151-156 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Ohnishi, et al: "Role of fibronectin-stimulated tumor cell migration in glioma invasion in vivo : clinical significance of fibronectin and fibronectin receptor expressed in human glioma tissues"Clin Exp Metastasis. 16. 729-741 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Ohnishi, et al: "Anovel modes of glioma cell invasion using organotypic brain slice culture"Cancer Res. 58. 2935-2940 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Ohnishi, et al: "In vitro and vivo potentiation of radiosensitivity of malignant gliomas by antisense inhibition of the RAD51 gene"Biochem Biophys Res Commun. 245. 319-324 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Hiraga, et al: "Telomerase activity and alterations in telomere length in human brain tumors"Cancer Res. 58. 2117-2125 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Ohnishi: "Adhesion molecules in the central nervous system. in : Immunological aspects of the nervous system and its diseases(Yoshida T, at al eds)"Nihon Igakukan, Tokyo. 131-139 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Ohnishi: "Quantitative analysis of glioma cell invasion by confocal laser scanning microscopy in a novel brain slice model"Biochem Biophys Res Commun. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Kanemura: "Isolation and expression analysis of a novel human homologue of the Drosophia glial cells missing (gcm) gene"FEBS Lett. 442. 151-156 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Ohnishi: "Role of fibronectin-stimulated tumor cell migration in glioma invasion in vivo: clinical significance of fibronectin and fibronectin receptor expressed in human glioma tissues"Clin Exp Metastasis. 16. 729-741 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Ohnishi: "A novel model of glioma cell invasion using organotypic brain slice culture"Cancer Res. 58. 2935-2940 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Ohnishi: "In vitro and in vivo potentiation of radiosensitivity of malignant gliomas by antisense inhibition of the RAD51 gene"Biochem Biophys Res Commun. 245. 319-324 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Hiraga: "Telomerase activity and alterations in telomere length in human brain tumors"Cancer Res. 58. 2117-2125 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 大西丘倫: "免疫学からみた神経系と神経疾患"日本医学館(東京). 374 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Ohnishi: "Role of fibronectin-stimulated tumor cell migration in glioma invasion in vivo:clinical significance of fibronection and fibronection receptor expressed in human glioma tissues." Clin Exp Metastasis. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Ohnishi: "A novel model of glioma cell invasion using organotypic brain slice culture." Cancer Res. 58. 2935-2940 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Ohnishi: "In vitro and in vivo potentiation of radiosensitivity of malignant gliomas by antisense inhinition of the RAD51 gene." Biochem Biophys Res Commun. 245. 319-324 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Hiraga: "Telomerase activity and alterations in telomere length in human brain tumors." Cancer Res. 58. 2117-2125 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Fukushima: "Integrin α3β1-mediated interaction with laminin-5 stimulates adhesion,migration,and invasion of malignant glioma cells." Int J Cancer. 76. 63-72 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大西丘倫: "免疫学からみた神経系と神経疾患" 日本医学館(東京)(印刷中), (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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