Cellular and Molecular Life Sciences CMLS

, Volume 57, Issue 1, pp 25–40

The plasminogen activation system in tumor growth, invasion, and metastasis

  • P. A. Andreasen*
  • R. Egelund
  • H. H. Petersen

DOI: 10.1007/s000180050497

Cite this article as:
Andreasen*, P., Egelund, R. & Petersen, H. CMLS, Cell. Mol. Life Sci. (2000) 57: 25. doi:10.1007/s000180050497

Abstract.

Generation of the serine proteinase plasmin from the extracellular zymogen plasminogen can be catalyzed by either of two other serine proteinases, the urokinase- and tissue-type plasminogen activators (uPA and tPA). The plasminogen activation system also includes the serpins PAI-1 and PAI-2, and the uPA receptor (uPAR). Many findings, gathered over several decades, strongly suggest an important and causal role for uPA-catalyzed plasmin generation in cancer cell invasion through the extracellular matrix. Recent evidence suggests that the uPA system is also involved in cancer cell-directed tissue remodeling. Moreover, the system also supports cell migration and invasion by plasmin-independent mechanisms, including multiple interactions between uPA, uPAR, PAI-1, extracellular matrix proteins, integrins, endocytosis receptors, and growth factors. These interactions seem to allow temporal and spatial reorganizations of the system during cell migration and a selective degradation of extracellular matrix proteins during invasion. The increased knowledge about the plasminogen activation system may allow utilization of its components as targets for anti-invasive therapy.

Key words. Serine proteinases; serpins; integrins; cell migration; anti-invasive therapy.

Copyright information

© Birkhäuser Verlag Basel, 2000

Authors and Affiliations

  • P. A. Andreasen*
    • 1
  • R. Egelund
    • 1
  • H. H. Petersen
    • 1
  1. 1.Cellular Protein Science Laboratory, Department of Molecular and Structural Biology, Aarhus University, 10C Gustav Wied’s Vej, 8000 Aarhus C (Denmark), Fax +45 8612 3178, e-mail: pa@mbio.aau.dkDK