研究課題
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.
すべて 2015 2014 その他
すべて 雑誌論文 (3件) (うち査読あり 3件、 オープンアクセス 3件) 学会発表 (8件) (うち招待講演 1件) 図書 (1件) 備考 (1件)
Leukemia
巻: 29 ページ: 145-56
10.1038/leu.2014.151.
Gastroenterology
巻: 148 ページ: 565-78
10.1053/j.gastro.2014.12.001.
Blood
巻: 123 ページ: 3932-42
10.1182/blood-2013-01-476747
http://stemcell-u-tokyo.org/scd/
