2014 Fiscal Year Annual Research Report
骨髄由来細胞を介した腫瘍血管新生及び増殖における血液線維素溶解系の機能解析
| Project Area | Integrative Research on Cancer Microenvironment Network |
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| Project/Area Number |
22112007
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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) |
2010-04-01 – 2015-03-31
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| Keywords | がん / 酵素 / 細胞・組織 / 発生・分化 / 生体・分子 |
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| Outline of Annual Research Achievements |
Extracellular matrix breakdown accomplished by e.g. the serine protease plasmin is crucial for cancer metastasis. We established that plasmin regulates inflammatory cell recruitment into tumor tissues of mice bearing cancers and into inflamed tissues of mice with inflammatory diseases. Mechanistically, plasmin modulates the activation status of various chemokines thereby enhancing inflammatory cell influx. Pharmacological inhibition of plasmin in e.g. prevented lymphoma cell progression and blocked intestinal bowel disease progression, a precondition for colon cancer (Munakata et al. Gastroenterology 2015; Sato et al. Leukemia 2015; Tashiro et al. Blood 2012). The observed clinical effects of plasmin inhibition were mediated due to the ability of plasmin to control the activation status of matrix metalloproteinases (MMPs).In addition, we demonstrated that the myeloid BM-derived CD11b+Jagged2+ cells regulate the epithelial-to mesenchymal transition (Caiado et al. PNAS 2013). In summary, plasmin by regulating the recruitment of inflammatory cells and by controlling the activation status of other proteases contributes to tumor progression.
In addition, we were able to establish a role for plasmin in regulating erythropoiesis (Okaji et al. Exp. Hematol 2012) and for MMPs include e.g. MMP-9 (Nakahara et al. Blood 2014) and membrane type1-MMP (Nishida et al. 2012) in controlling normal or malignant hematopoiesis.
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| Research Progress Status |
26年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
26年度が最終年度であるため、記入しない。
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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
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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
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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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