1994 Fiscal Year Final Research Report Summary
The role of matrix metalloproteinases for glioma cell invasion.
| Project/Area Number |
05671151
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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 | Fukui Medical School |
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Principal Investigator |
KUBOTA Toshihiko Fukui Medical School, Neurosurgery, Professor, 医学部, 教授 (70092781)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Kazufumi Fukui Medical School, Neurosurgery, Assistant, 医学部, 助手 (60187177)
KABUTO Masanori Fukui Medical School, Neurosurgery, Lecturer, 医学部, 講師 (80169599)
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| Project Period (FY) |
1993 – 1994
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| Keywords | glioma / matrix metalloproteinase / invasion / extracellular matrix |
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| Research Abstract |
We investigated the role of matrix metalloproteinases (MMPs) for glioma cell invasion. We demonastrated a good correlation of MMP-2 (72 kD gelatinase/type IV collagenase = gelatinase A) production with cellular invasion in vitro by malignant glioma cells. Malignant glioma tissues obtained from surgical specimens also showed high MMP activity and positive immunostaining for MMPs including MMP-1 (interstitial collagenase) , MMP-2, MMP-3 (stromelysin-1) and MMP-9 (92 kD gelatinase/type IV collagenase) . These results suggest that MMPs play an important role in glioma cell invasion in vivo. MMP activity is regulated by natural inhibitors in the extracellular milieu, of which two related but distinct inhibitors, designated TIMP-1 and TIMP-2, are considered to be major regulators of MMPs. We demonstrated that an increased expression of TIMP-1 is associated with the malignant progression of gliomas. This result was unexpected because of the inhibitory effects of TIMP-1 on tumor cell invasion. However, recently it has been reported that TIMP-1 exerts a growth-enhancing effect in addition to its role as a MMP inhibitor. We showed that human recombinant TIMP-2, but not TIMP-1, inhibited the glioma cells in vitro. In human glioma tissues, TIMP-2 may thus play a more imortant role in tumor cell invasion. Studies on the expression of TIMP-2 in human gliomas are now underway in our laboratories. We demonstrated that captopril inhibited the invasiveness of malignant glioma cells due to its MMP inhibitory activity. Animal experiments using nude mice transplanted with human gliomas are currently underway in our laboratory to examine the effect of captopril on glioma cell invasion in vivo.
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