title: Cancer therapy targeting the fibrinolytic system.
abstract: The tumor microenvironment is recognized as a key factor in the multiple stages of cancer progression, mediating local resistance, immune-escape and metastasis. Cancer growth and progression require remodeling of the tumor stromal microenvironment, such as the development of tumor-associated blood vessels, recruitment of bone marrow-derived cells and cytokine processing. Extracellular matrix breakdown achieved by proteases like the fibrinolytic factor plasmin and matrix metalloproteases is necessary for cell migration crucial for cancer invasion and metastasis. Key components of the fibrinolytic system are expressed in cells of the tumor microenvironment. Plasmin can control growth factor bioavailability, or the regulation of other proteases leading to angiogenesis, and inflammation. In this review, we will focus on the role of the fibrinolytic system in the tumor microenvironment summarizing our current understanding of the role of the fibrinolytic factors for the modulation of the local chemokine/cytokine milieu, resulting in myeloid cell recruitment, which can promote neoangiogenesis.
authors.affiliation: Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Atopy (Allergy) Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: heissig@ims.u-tokyo.ac.jp.
authors.forename: Beate
authors.initials: B
authors.lastname: Heissig
authors.affiliation: Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Salita
authors.initials: S
authors.lastname: Eiamboonsert
authors.affiliation: Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Salama
authors.affiliation: Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimazu
authors.affiliation: Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Douaa
authors.initials: D
authors.lastname: Dhahri
authors.affiliation: Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Munakata
authors.affiliation: Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tashiro
authors.affiliation: Division of Stem Cell Regulation, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Center for Genome and Regenerative Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hattori
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D018450:Disease Progression; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D022423:Myeloid Cells / Q000187:drug effects / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D005343:Fibrinolytic Agents
keywords: CXCL5; Cancer; Chemokine; Inflammation; MCP-1; Matrix metalloproteinase; Microenvironment; Plasmin