Brain Tumor Pathology

, Volume 19, Issue 2, pp 69–76 | Cite as

Tracking cell invasion of human glioma cells and suppression by anti-matrix metalloproteinase agent in rodent brain-slice model

  • Daizo Yoshida
  • Kunihiro Watanabe
  • Masahiro Noha
  • Hiroshi Takahashi
  • Akira Teramoto
  • Yuichi Sugisaki
Original Article

Abstract

Persistent expression of green fluorescent protein (GFP) in human malignant glioma cell clones (U87MG, U251MG, and U373MG) was established using the pEGFP-C1 vector. Tumor spheroid was implanted into the caudate nucleus-putamen of a severely compromised immunodeficient (SCID) mouse brain slice. To allow quantitative assessment of tumor cell invasion, the invasion area index was measured on days 1, 3, 5, and 7 by a fluorescence stereomicroscope and an image analyzer in the presence of varying concentrations of SI-27. In the control group (0μg/ml), all glioma cell lines invaded in a fingerlike fashion, reaching the contralateral hemisphere via the corpus callosum. SI-27 at concentrations of 10, 50, or 100 μg/ml significantly suppressed the index on days 5 and 7 in a dose-dependent manner, whereas 1 μg/ml had no effect. Laser confocal microscopy indicated that the tumor cells penetrated through the brain slice. This model enabled unequivocal periodic tracking of individual invading tumor cells in the normal brain. The significant suppression of glioma cell invasion by SI-27 indicates that anti-matrix metalloproteinase (MMP) treatment may represent an important future therapeutic strategy for malignant cerebral neoplasms.

Key words

Brain slice Cell invasion Green fluorescent protein Malignant glioma Matrix metalloproteinase 

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Copyright information

© The Japan Society of Brain Tumor Pathology 2002

Authors and Affiliations

  • Daizo Yoshida
    • 1
  • Kunihiro Watanabe
    • 1
  • Masahiro Noha
    • 1
  • Hiroshi Takahashi
    • 1
  • Akira Teramoto
    • 1
  • Yuichi Sugisaki
    • 2
  1. 1.Department of NeurosurgeryNippon Medical SchoolTokyoJapan
  2. 2.Central Institute for Electron MicroscopyNippon Medical SchoolTokyoJapan

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