1999 Fiscal Year Final Research Report Summary
Analysis of the molecular mechanism of glioma invasion by using a brain slice invasion model
| Project/Area Number |
10671297
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
OHNISHI Takanori Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70233210)
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| Co-Investigator(Kenkyū-buntansha) |
IZUMOTO Shuichi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手
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| Project Period (FY) |
1998 – 1999
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| Keywords | malignant glioma / invasion model / tumor invasion / brain slice / matrix metalloproteinase / confocal laser scanning microscopy |
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| 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.
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