| Co-Investigator(Kenkyū-buntansha) |
KOGA Hisao SAGA MEDICAL SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (30153513)
SHIRAISHI Tetsuya SAGA MEDICAL SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (70206275)
FUKUYAMA Kouzou SAGA MEDICAL SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (60238516)
HIROTSU Tatsumi SAGA MEDICAL SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (00244012)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
The integrin family is a group of cell surface receptors against extracellular matrix proteins, such as collagen, fibronectin and laminin. They make a complex with membrane conjugated proteins, such as tarin and vinculin, which connected with cyteskeletone proteins ; actine and myosine. The actine is well known as a partner of glial cell specific intermediate filament ; CFAP,in glial cells. That is the various signals from the extracellular matrix go through integrins into cytoplasm, finally transduce to GFAP,which modulates the cellular molphology and mobility.
In normal central nervous system, it is observed the expression of a2-, a3-, a6-, b1, and b4-subunit of integrin, but no expression of a4-, a5-, av-, b2-, and b3-subunit. It has been reported that the overexpression of a3-and b1-subunit and abnormal expression of a5-, av-, and b3-subunit were detected in human glioma cells. In this study we revealed the deceased expression of a5- and a6-subunit specifically in some invasive glio
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mas, which were deficient with GFAP.These cells produced increased volume of type IV collagenase and stromelysin, and decreased volume of their inhibitors ; TIMP-1 and TIMP-2. It seemed very interesting that the decreased expression of a5-and a6-subunit was associated with the deficient of the GFAP in glial tumors.
It is observed many GFAP processes are anchoring the vessells in glial tumor. Most of them are MIB-1 negative, non-proliferating cells. The MIB-1 positive, proliferating cells are usually detach from vessels, and migrate into brain parenchyme. We hypothesized that the tumor cells without certain integrins easily detach from the extracellular matrix, and migrate, and invade and proliferate in brain parenchyme. In this study we observed invasive glioma cells which are deficient with a5-and a6-subunit produced increased amount of collagenases, also expressed fewer amount of GFAP.This fact can explain the hypothesis that the integrin mediate the anchorage dependent growth and migration suppression. Less
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