Cellular and Molecular Life Sciences CMLS

, Volume 60, Issue 3, pp 463–473 | Cite as

Role of plasminogen activator-plasmin system in tumor angiogenesis

  • J. M. Rakic
  • C. Maillard
  • M. Jost
  • K. Bajou
  • V. Masson
  • L. Devy
  • V. Lambert
  • J. M. Foidart
  • A. Noël

Abstract:

New blood formation or angiogenesis has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization. Angiogenesis is associated with important extracellular remodeling involving different proteolytic systems among which the plasminogen system plays an essential role. It belongs to the large serine proteinase family and can act directly or indirectly by activating matrix metalloproteinases or by liberating growth factors and cytokines sequestered within the extracellular matrix. Migration of endothelial cells is associated with significant upregulation of proteolysis and, conversely, immunoneutralization or chemical inhibition of the system reduces angiogenesis in vitro. On the other hand, genetically altered mice developed normally without overt vascular anomalies indicating the possibility of compensation by other proteases in vivo. Nevertheless, they have in some experimental settings revealed unanticipated roles for previously characterized proteinases or their inhibitors. In this review, the complex mechanisms of action of the serine proteases in pathological angiogenesis are summarized alongside possible therapeutic applications.

Key words: Plasminogen; angiogenesis; extracellular matrix; PAI-1; proteinase inhibitor. 

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Copyright information

© Birkhäuser Verlag, 2003

Authors and Affiliations

  • J. M. Rakic
    • 1
  • C. Maillard
    • 2
  • M. Jost
    • 2
  • K. Bajou
    • 2
  • V. Masson
    • 2
  • L. Devy
    • 2
  • V. Lambert
    • 2
  • J. M. Foidart
    • 2
  • A. Noël
    • 2
  1. 1.Department of Ophthalmology, CHU, Sart-Tilman, 4000 Liège (Belgium)BE
  2. 2.Laboratory of Tumor and Developmental Biology, University of Liège, Tour de Pathologie (B23), Sart-Tilman, 4000 Liège (Belgium), Fax +3243662936, e-mail: agnes.noel@ulg.ac.beBE

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