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Establishment of glioma invasion model by using the three-dimensional brain organotypic culture

Research Project

Project/Area Number 08671581
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 Medical School, Assistant Professor, 医学部, 助手 (70233210)

Co-Investigator(Kenkyū-buntansha) IZUMOTO Shuichi  Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
HIRAGA Shoju  Osaka University Medical School, Assistant Professor, 医学部, 助手 (40243232)
HAYAKAWA Toru  Osaka University Medical School, Professor, 医学部, 教授 (20135700)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsglioma / tumor invasion / motility / brain organotypic culture / invasion model / cell adhesion molecule / 神経接着因子 / 脳切片培養
Research Abstract

Glioma invasion model was established by using an organotypic culture of rat brains. Brain slices prepared from 2-day-old rat neonates were maintained in culture at the interface between air and the culture medium. The slices were placed on double-layred membranes consisting of an 8mm pore-size polycarbonate membrane and a 0.4mm pore-size membrane. The organotypic cytoarchitecture in cultured brain slices remained well preserved while the neuronal viability was kept intact for over two months When C6 glioma spheroids were cocultured with brain slices, the tumor cells migrated in a scattered fashion around the spheroids. The cell migration was strongly stimulated by exogenous L1 or GMF-I,while fibronectin, tenascin and GMF-II had little or no effect. When C6 glioma cells placed on the brain slices were incubated while being stimulated by L1-transfected fibroblast cells for 2 days, many more tumor cells invaded and reached the bottom of the upper membrane. This L1-stimulated glioma cell invasion into brain slices was significantly inhibited by an anti-L1 antibody. The present invasion model, which mimics the in vivo conditions of the CNS,may make it possible to analyze actual events of glioma cell invasion in normal brains in situ.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] S.Hiraga, et al: "Telomerase activity and alterations in telomere length in human brain tumors." Cancer Res. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Fukushima, et al: "Integrin α3β1-mediated interaction with laminin-5 stimulates adhesion,migration and invasion of malignant glioma cells." Int J Cancer. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Taki, et al: "In vivo etoposide-resistant C6 glioma cell line : significance of altered DNA topoisomerase II activity in multi-drug resistance." J Neuro-Oncol. 36. 41-53 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Tsuzuki, et al: "Neural cell adhesion molecule L1 in gliomas : correlation with TGF-β and p53." J Clin Pathol. 51. 13-17 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Ohnishi, et al: "Fibronectin-mediated cell migration promotes glioma cell invasion through chemokinetic activity." Clin Exp Metastasis. 15. 538-546 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Izumoto, et al: "Microsatellite instability and mutated type II transforming growth factor-b receptor gene in gliomas." Cancer letters. 112. 251-256 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Ohnishi, et al: "Brain Tumor Research and Therapy" Springer-Verlag,Tokyo, 109-118 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Hiraga, et al: "Telomerase activity and alterations in telomere length in human brain tumors." Cancer Res. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Fukushima, et al: "Integrin alpha3beta1-mediated interaction with laminin-5 stimulates adhesion, migration and invasion of malignant glioma cells." Int J Cancer. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Taki, et al: "In vivo etoposide-resistant C6 glioma cell line : significance of altered DNA topoisomerase II activity in multi-drug resistance." J Neuro-Oncol. 36. 41-53 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Tsuzuki, et al: "Neural cell adhesion molecule L1 in gliomas : correlation with TGF-beta and p53." J Clin Pathol. 51. 13-17 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Ohnishi, et al: "Fibronectin-mediated cell migration promotes glioma cell invasion through chemokinetic activity." Clin Exp Metastasis. 15. 538-546 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Izumoto, et al: "Microsatellite instability and mutated type II transforming growth factor-beta receptor gene in gliomas." Cancer Letters. 112. 251-256 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Ohnishi, et al.: Expression and biological functions of L1 cell adhesion molecule in malignant glioma cells. Brain Tumor Research and Therapy Springer-Verlag, Tokyo, 109-118 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Hiraga, et al: "Telomerase activity and alterations in telomere length in human brain tumors." Cancer Res. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Fukushima, et al: "Integrin α3β1-mediated interaction with laminin-5 stimulates adhesion,migration and invasion of malignant glioma cells." Int J Cancer. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Taki, et al: "In vivo etoposide-resistant C6 glioma cell line:significance of altered DNA topoisomerase II activity in multi-drug resistance." J Neuro-Oncol. 36. 41-53 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Tsuzuki, et al: "Neural cell adhesion molecule L1 in gliomas:correlation with TGF-β and p53." J Clin Pathol. 51. 13-17 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Ohnishi, et al: "Fibronectin-mediated cell migration promotes glioma cell invasion through chemokinetic activity." Clin Exp Metastasis. 15. 538-546 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Izumoto, et al: "Microsatellite instability and mutated type II transforming growth factor-b receptor gene in gliomas." Cancer letters. 112. 251-256 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Ohnishi, et al: "Brain Tumor Research and Therapy" Springer-Verlag,Tokyo, 109-118 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Ohnishi,et al: "Fibronectin-mediated cell migration promotes glioma cell invasion through chemokinetic activity" Clin Exp Metastasis. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Izumoto,et al: "Microsatellite instability and mutated type II transfarming growth factor-b receptor gene in gliomas." Cancer letters. 112. 251-256 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Hiraga,et al: "Establishment of spontaneously immortalized rat type 1 astrglial cell lines : the role of p53 in astroglial carcinogenesis." GLIA. 18. 185-199 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Taki,et al: "Antisense inhibition of the RAD51 enhances radiosensitivity." Biochem Biophys Rec Commun. 223. 434-438 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Izumoto,et al: "Gene expression of neural cell adhesion L1 in malignant gliomas and biological significance of L1 in glioma invasion." Cancer Res. 56. 1440-1444 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Yamamoto,et al: "Abrogation of lung metastasis of human fibrosarcoma cells by ribozyme-mediated suppression of integrin a6 subunit expression." Int J cancer. 65. 519-524 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Ohnishi,et al: "Brain Tumor Research and Therapy" Springer-Verlag,Tokyo, 109-118 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Izumoto,et al: "Brain Tumor Research and Therapy" Springer-Verlag,Tokyo, 103-107 (1995)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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