caa a22 4500 60617625X CHVBK 20210128100746.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00018-015-2035-7 doi (NATIONALLICENCE)springer-10.1007/s00018-015-2035-7 Role of mesenchymal stem cell-derived fibrinolytic factor in tissue regeneration and cancer progression [Elektronische Daten] [Beate Heissig, Douaa Dhahri, Salita Eiamboonsert, Yousef Salama, Hiroshi Shimazu, Shinya Munakata, Koichi Hattori] Tissue regeneration during wound healing or cancer growth and progression depends on the establishment of a cellular microenvironment. Mesenchymal stem cells (MSC) are part of this cellular microenvironment, where they functionally modulate cell homing, angiogenesis, and immune modulation. MSC recruitment involves detachment of these cells from their niche, and finally MSC migration into their preferred niches; the wounded area, the tumor bed, and the BM, just to name a few. During this recruitment phase, focal proteolysis disrupts the extracellular matrix (ECM) architecture, breaks cell-matrix interactions with receptors, and integrins, and causes the release of bioactive fragments from ECM molecules.MSC produce a broad array of proteases, promoting remodeling of the surrounding ECM through proteolytic mechanisms. The fibrinolytic system, with its main player plasmin, plays a crucial role in cell migration, growth factor bioavailability, and the regulation of other protease systems during inflammation, tissue regeneration, and cancer. Key components of the fibrinolytic cascade, including the urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), are expressed in MSC. This review will introduce general functional properties of the fibrinolytic system, which go beyond its known function of fibrin clot dissolution (fibrinolysis). We will focus on the role of the fibrinolytic system for MSC biology, summarizing our current understanding of the role of the fibrinolytic system for MSC recruitment and the functional consequences for tissue regeneration and cancer. Aspects of MSC origin, maintenance, and the mechanisms by which these cells contribute to altered protease activity in the microenvironment under normal and pathological conditions will also be discussed. Springer Basel, 2015 Plasmin nationallicence uPAR nationallicence uPA nationallicence Integrin nationallicence Cancer nationallicence Tissue-type plasminogen activator nationallicence Wound healing nationallicence MMP nationallicence Microenvironment nationallicence Niche nationallicence Hematopoiesis nationallicence Chemokine nationallicence TGF-b nationallicence Colorectal cancer nationallicence Hypoxia nationallicence MSC : Mesenchymal stem cells nationallicence ECM : Extracellular matrix nationallicence BM : Bone marrow nationallicence IL : Interleukin nationallicence VEGF-A : Vascular endothelial growth factor-A (VEGF-A) nationallicence MMP : Matrix metalloproteinase nationallicence uPAR : Urokinase-type plasminogen activator receptor nationallicence PAI-1 : Plasminogen activator inhibitor-1 nationallicence uPA : Urokinase-type plasminogen activator nationallicence CD : Cluster of differentiation nationallicence FGF-2 : Fibroblast growth factor-2 nationallicence TGF-β : Transforming growth factor-β nationallicence tPA : Tissue-type plasminogen activator nationallicence HSC : Hematopoietic stem cell nationallicence MCP-1 : Monocyte chemoattractant protein-1 nationallicence suPAR : Soluble uPAR nationallicence PA : Plasminogen activator nationallicence HIF-1α : Hypoxia inducible factor α nationallicence HGF : Hepatocyte growth factor nationallicence CRC : Colorectal cancer nationallicence HER 2 : Human epidermal growth factor receptor 2 nationallicence Heissig Beate Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut Dhahri Douaa Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut Eiamboonsert Salita Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut Salama Yousef Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut Shimazu Hiroshi Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut Munakata Shinya Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut Hattori Koichi Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut Cellular and Molecular Life Sciences Springer International Publishing 72/24(2015-12-01), 4759-4770 1420-682X 72:24<4759 2015 72 18 https://doi.org/10.1007/s00018-015-2035-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-2035-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Heissig Beate Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut NATIONALLICENCE 700 1- Dhahri Douaa Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut NATIONALLICENCE 700 1- Eiamboonsert Salita Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut NATIONALLICENCE 700 1- Salama Yousef Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut NATIONALLICENCE 700 1- Shimazu Hiroshi Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut NATIONALLICENCE 700 1- Munakata Shinya Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut NATIONALLICENCE 700 1- Hattori Koichi Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer International Publishing 72/24(2015-12-01), 4759-4770 1420-682X 72:24<4759 2015 72 18