| Project/Area Number |
06671389
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 Medical School, Assistant, 医学部, 助手 (70233210)
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| Co-Investigator(Kenkyū-buntansha) |
SAITOH Youichi Osaka University Medical School, Assistant, 医学部, 助手 (20252661)
HIRAGA Shoju Osaka University Medical School, Assistant, 医学部, 助手 (40243232)
HAYAKAWA Toru Osaka University Medical School, Prefessor, 医学部, 教授 (20135700)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Brain tumor / Malignant glioma / Tumor invasion / Cell motility / Cell adhesion / 浸潤 / 細胞外マトリックス / 細胞接着因子 |
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| Research Abstract |
The molecular mechanism of tumor invasion in malignant gliomas remains unknown. In order to clarify a biosignal of the tumor invasion, we have focused on cell adhesion and motility of glioma cells and succeeded in purification of glioma motility factors (GMFs) which stimulate both chemotactic and chemokinetic migration of the producer cells. In the present study, we have investigated a possible role of GMF in glioma invasion and analyzed the structure of GMF to examine a regulatory mechanism in glioma cell motility. Invasiveness of glioma cells was assessed by in vitro chemoinvasion assay and an in vivo tumor-implanted model. Sequence analysis of GMF was performed by digestion of the GMF with lysylendopeptidase. Since the GMF showed a partial homology to fibronectin (FN), immunoblot anayses of the GMF were carried out using several antibodies which recognized various domains of FN.There were two species of GMF,ie, GMF-I and GMF-II with a molecular mass of 145 K and 165 K,respectively. The GMFs had cell binding and heparin binding domains of FN and also expressed ED (extra-domain)-regions, which were seen in the oncofetal FN,in a different way between GMF-I and -II.GMF-I expressing only ED-B domain showed migration activity 5 to 10 times stronger than GMF-II expressing both ED-A and ED-B domains. The GMF-induced migration of glioma cells correlated well with in vitro invasiveness of these cells and addition of GMF to glioma cells enhanced the invasiveness of the cells. In addition, coexistance of GMF with glioma cells which were implanted in rat brains promoted the migration of the cells much more than glioma cell only. These results suggest that GMFs paly an important role in glioma invasion and a difference of expression in ED-regions of GMFs may regulate a cell motility in glioma cells.
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