計画研究
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.
26年度が最終年度であるため、記入しない。
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 1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/
