2014 Fiscal Year Final Research Report
Multifunctional role of Membrane-type 1 matrix metalloproteinase in multiple myeloma
Project/Area Number |
24591382
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | The University of Tokyo |
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 / 発現制御 / 酵素 |
Outline of Final Research Achievements |
Multiple myeloma (MM) is a B-cell malignancy characterized by the monoclonal proliferation of plasma cells in the bone marrow (BM). In the initial stages of disease establishment, MM cells reside in a hypoxic BM microenvironment. The long-term objective of this proposal is to examine the role of membrane type-1-matrix metalloproteinase (MT1-MMP) in the regulation of normal B cell development and malignant plasma cell growth in models of MM. MT1-MMP is expressed in MM cells, and cells of the MM microenvironment. Stroma cells produce cytokines. MT1-MMP is required for normal B cell development. Mechanistically we showed that MT1-MMP drives HIF-1-mediated activation of cytokines like Kit ligand, stromal cell-derived factor-1, and interleukin-7. Most cell line-based MM models show BM infiltration of MM cells. We established a novel murine model that mimics various aspects of clinical signs of MM, which will help to understand the interaction between malignant plasma and stroma cells.
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Free Research Field |
血液学、腫瘍学、幹細胞生物学、免疫学
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