Functional analysis of the fibrinolytic system in bone marrow-derived cell mediated tumor angiogenesis and growth

2014 Fiscal Year Final Research Report

• Project Area: Integrative Research on Cancer Microenvironment Network
• Project/Area Number: 22112007
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: HEISSIG Beate 東京大学, 医科学研究所, 准教授 (30372931)
• Co-Investigator(Renkei-kenkyūsha): HATTORI Koichi 順天堂大学, 医学(系)研究科, 特任先任准教授 (10360116)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: がん / 酵素 / 細胞・組織 / 発生・分化 / 生体・分子

Outline of Final Research Achievements

The tumor microenvironment includes hematopoietic cells, endothelial cells, and cancer-associated fibroblasts. Hematopoietic-myeloid cells promote cancer growth by stimulating angiogenesis (formation of new blood vessels). Plasmin inhibition (pharmacological and genetic) prevented T cell lymphoma growth and diminished matrix metalloproteinase-9 (MMP-9)-dependent CD11b+F4/80+ myeloid cell infiltration into lymphoma tissues. Inflammatory bowel disease (IBD) and here especially ulcerative colitis patients are endowed with a high of developing colorectal cancer. Plasmin regulated IBD progression in models of IBD by activating MMP-9 and enhancing myeloid cell influx. Plasminogen activation not only activated other proteases like MMP-9, but also mobilized marrow derived CD45+CD11b+VEGFR-1+ cells, which promoted neovascularization. In summary, we have established a critical role of the fibrinolytic system for regulating the cellular composition of the tumor microenvironment.

Free Research Field

血液学、腫瘍学、幹細胞生物学、免疫学