| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| 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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