2002 Fiscal Year Final Research Report Summary
Effects of HAl-i andHAI-2 on the growth and invasion of human glioblastoma cells
| Project/Area Number |
13671449
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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 | Miyazaki Medical College |
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Principal Investigator |
NAKANO Shinichi Miyazaki Medical College, Neurosurgery, Associate Professor, 医学部, 助教授 (80189000)
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| Co-Investigator(Kenkyū-buntansha) |
NUKI Yoshitsugu Miyazaki Medical College, Neurosurgery, Instructor, 医学部, 助手 (10325756)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Hepatocyte growth factor activator inhibitor (HAI) / HAI-1 / HAI-2 / glioblastoma |
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| Research Abstract |
Hepatocyte growth factor activator inhibitor (HAl) was initially identified as a potent endogenous inhibitor of hepatocyte growth factor activator (HGFA) that is responsible for the activation of hepatocyte growth factor/scatter factor. To date two kinds of HAI have been identified, namely HAI-1 and HAI-2. Both are Kunitz-type serine proteinase inhibitors and inhibit not only HGFA but also other serine proteinases such as plasmin and trypsin. Notably, each HAI has a transmembrane domain near the carboxyl terminal end, and thus, HAI is an integral-membrane proteinase inhibitor that must have important regulatory role on the cellular surface. To explore the possible role of HAI-1 and HAI-2 in invasive growth of tumor cells, we analyzed the effects of experimental over-expression of each HAI on glioblastoma (GBM), a malignant brain tumor that is highly invasive. Two cultured human GBM cell lines (U251 and YKG-1) were stably transfected with an expression vector harboring human HAI-1 or HAI-2 cDNA. Subsequent in vitro analyses indicated that the over-expression of HAI-2 significantly suppressed the fibrinolytic activity, as well as the invasion into the fibrin gel, of both GBM cell lines. On the other hand, the expression of HAI-1 showed much less effect relative to HAI-2 on the fibrinolytic activity of GBM cells. Then, we analyzed the effects of HAIs on in vivo invasive growth of these cell lines. The GBM cells were injected into the nude mice brain. Eight weeks after the injection, the mice were sacrificed and necropsied in order to determine the development of tumor. Rather surprisingly, HAI-2-transfected clones showed enhanced frequency of the tumor formation in vivo and formed larger tumor than control clones. These results indicated that HAI, particularly HAI-2, might have undetermined important function on the survival and/or growth of tumor cells in vivo, which is dependent or independent of its proteinase-inhibitory activity.
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Research Products
(3 results)
