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

Cell Mol Life Sci. 2000 Jan 20;57(1):25-40. doi: 10.1007/s000180050497.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Division
  • Cell Movement
  • Fibrinolysin / metabolism
  • Humans
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Metastasis*
  • Neoplasms / enzymology*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Plasminogen / metabolism*
  • Plasminogen Activators / metabolism
  • Plasminogen Inactivators / metabolism
  • Signal Transduction
  • Vitronectin / metabolism


  • Plasminogen Inactivators
  • Vitronectin
  • Plasminogen
  • Plasminogen Activators
  • Fibrinolysin