Plasmin inhibitor reduces T-cell lymphoid tumor growth by suppressing matrix metalloproteinase-9-dependent CD11b(+)/F4/80(+) myeloid cell recruitment

Leukemia. 2012 Feb;26(2):332-9. doi: 10.1038/leu.2011.203. Epub 2011 Sep 20.


Activation of the fibrinolytic system during lymphoma progression is a well-documented clinical phenomenon. But the mechanism by which the fibrinolytic system can modulate lymphoma progression has been elusive. The main fibrinolytic enzyme, plasminogen (Plg)/plasmin (Plm), can activate matrix metalloproteinases (MMPs), such as MMP-9, which has been linked to various malignancies. Here we provide the evidence that blockade of Plg reduces T-cell lymphoma growth by inhibiting MMP-9-dependent recruitment of CD11b(+)F4/80(+) myeloid cells locally within the lymphoma tissue. Genetic Plg deficiency and drug-mediated Plm blockade delayed T-cell lymphoma growth and diminished MMP-9-dependent CD11b(+)F4/80(+) myeloid cell infiltration into lymphoma tissues. A neutralizing antibody against CD11b inhibited T-cell lymphoma growth in vivo, which indicates that CD11b(+) myeloid cells have a role in T-cell lymphoma growth. Plg deficiency in T-cell lymphoma-bearing mice resulted in reduced plasma levels of the growth factors vascular endothelial growth-A and Kit ligand, both of which are known to enhance myeloid cell proliferation. Collectively, the data presented in this study demonstrate a previously undescribed role of Plm in lymphoproliferative disorders and provide strong evidence that specific blockade of Plg represents a promising approach for the regulation of T-cell lymphoma growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifibrinolytic Agents / pharmacology*
  • CD11b Antigen / immunology*
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Lymphoma, T-Cell / enzymology
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / pathology*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Plasminogen / genetics
  • Plasminogen / physiology
  • Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antifibrinolytic Agents
  • CD11b Antigen
  • DNA Primers
  • Plasminogen
  • Matrix Metalloproteinase 9