| Project/Area Number |
10044244
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SEIKI Motoharu Inst. Med. Sci., Univ. Tokyo, Prof., 医科学研究所, 教授 (10154634)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Yoshifumi Inst. Med. Sci., Univ. Tokyo, Assis. Prof., 医科学研究所, 助手 (70292852)
OKADA Akio Inst. Med. Sci., Univ. Tokyo, Assis. Prof., 医科学研究所, 助手 (00233320)
トンプソン エリク ビンセント医科学研究所, 室長
ゴールドパーグ グリコリ ワシントン大学, 医学部, 教授
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Extracellular matrix / Invasion and metastasis / Matrix metalloproteinase / Gelatinase A / MT-MMP / MMP / MT-1-MMP / ゼラチナーゼA / がんの浸潤・転移 |
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| Research Abstract |
(1) Malignant melanoma cells degrade gelatin gel beneath the cells by extending protrusions called invadpodia. We foud that MT1-MMP localizes on the invadpodia. To monitor the cell surface. MT1-MMP more easily, we made MT1MMP fused with GFP and expressed it in the melanoma cells. Localization of GFP/MT1-MMP was clearly observed at invade podia where actin bundle can be seen. MT1-MMP was also detected along with actin stress fibers when it is expressed in on invasive CHO-K1 cells. Thus, localization of MT1-nMMP seems to be regulated through actin cytoskelton within the cells.
(2) MT1-MMP activates pro-gelatinase Aby introducing cleavage in the propeptide domain in vitro. Expression of MT1-MMP in cultured cells induce cell-mediated activation of pro-gelatinase A. To confirm whether MT1-MMP can act as the activator of pro-gelatinase A in vivo, we generatedgene knockout mice by substituting the 1st to 4th exons of mouse genome to LacZ and Neo gene. Wild type mouse express MT1-MMP at high levels in various tissue during embryogenesis and activation of pro-gelatinase A in the tissue can be observed. In the knockout mice, however, such actibation of pro-gelatinase A could not be observed anymore. Thus, we conclued that MT1-MMP is the physiological activator of pro-gelatinase A.
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