2014 Fiscal Year Annual Research Report
多発性骨髄腫病態における膜型マトリックスメタロプロテアーゼ活性の機能解明
| Project/Area Number |
24591382
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HEISSIG Beate 東京大学, 医科学研究所, 准教授 (30372931)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 生体分子 / 細胞・組織 / 発言制御 / 酵素 |
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| Outline of Annual Research Achievements |
Multiple myeloma (MM) is a B-cell malignancy characterized by the monoclonal proliferation of plasma cells (PCs) in the bone marrow causing severe osteolytic lesions in various bones of patients. The protease membrane type-1-matrix metalloproteinase (MT1-MM) is expressed in PCs, and cells of the MM microenvironment. The activation status of MT1-MMP can be altered by the fibrinolytic factor plasmin. Fibrinolytic factors were suggested as prognostic markers in MM. We established a murine model of MM where we could achieve high infiltration of MM cells into the bone marrow of tested animals. This is important as a hallmark of MM is the high homing capacity of PCs into bones. We could show that upregulated various fibrinolytic factors during disease progression in murine models of MM in vivo. Although pharmacological plasmin inhibition suppressed MT1-MMP expression, the tested dose of a recently developed plasmin inhibitor in our study was not able to prevent MM growth progression in vivo. Further studies will be required to test whether dose escalation of the plasmin inhibitor can prevent disease progression in MM murine models.
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Research Products
(13 results)
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[Journal Article] Inhibition of plasmin attenuates murine acute graft-versus-host disease mortality by suppressing the matrix metalloproteinase-9-dependent inflammatory cytokine storm and effector cell trafficking.2015
Author(s)
A Sato, C Nishida, K Sato-Kusubata, M Ishihara, Y Tashiro, I Gritli, H Shimazu, S Munakata, H Yagita, K Okumura, Y Tsuda, Y Okada, A Tojo, H Nakauchi, S Takahashi, B Heissig and K Hattori
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Journal Title
Leukemia
Volume: 29
Pages: 145-56
DOI
Peer Reviewed / Open Access
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[Journal Article] Inhibition of Plasmin Protects Against Colitis in Mice by Suppressing Matrix Metalloproteinase 9-Mediated Cytokine Release From Myeloid Cells.2015
Author(s)
Munakata S, Tashiro Y, Nishida C, Sato A, Komiyama H, Shimazu H, Dhahri D, Salama Y, Eiamboonsert S, Takeda K, Yagita H, Tsuda Y, Okada Y, Nakauchi H, Sakamoto K, Heissig B, Hattori K.
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Journal Title
Gastroenterology
Volume: 148
Pages: 565-78
DOI
Peer Reviewed / Open Access
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[Journal Article] Hes1 promotes blast crisis in chronic myelogenous leukemia through MMP-9 upregulation in leukemic cells.2014
Author(s)
Nakahara F, Kitaura J, Uchida T, Nishida C, Togami K, Inoue D, Matsukawa T, Kagiyama Y, Enomoto Y, Kawabata KC, Chen-Yi L, Komeno Y, Izawa K, Oki T, Nagae G, Harada Y, Harada H, Otsu M, Aburatani H, Heissig B, Hattori K, Kitamura T.
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Journal Title
Blood
Volume: 123
Pages: 3932-42
DOI
Peer Reviewed / Open Access
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