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      The urokinase-type plasminogen activator system in cancer metastasis: a review.

      1 , , ,
      International journal of cancer
      Wiley

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          Abstract

          The urokinase-type plasminogen activator (u-PA) system consists of the serine proteinases plasmin and u-PA; the serpin inhibitors alpha2-anti-plasmin, PAI-1 and PAI-2; and the u-PA receptor (u-PAR). Two lines of evidence have strongly suggested an important and apparently causal role for the u-PA system in cancer metastasis: results from experimental model systems with animal tumor metastasis and the finding that high levels of u-PA, PAI-1 and u-PAR in many tumor types predict poor patient prognosis. We discuss here recent observations related to the molecular and cellular mechanisms underlying this role of the u-PA system. Many findings suggest that the system does not support tumor metastasis by the unrestricted enzyme activity of u-PA and plasmin. Rather, pericellular molecular and functional interactions between u-PA, u-PAR, PAI-1, extracellular matrix proteins, integrins, endocytosis receptors and growth factors appear to allow temporal and spatial re-organizations of the system during cell migration and a selective degradation of extracellular matrix proteins during invasion. Differential expression of components of the system by cancer and non-cancer cells, regulated by paracrine mechanisms, appear to determine the involvement of the system in cancer cell-directed tissue remodeling. A detailed knowledge of these processes is necessary for utilization of the therapeutic potential of interfering with the action of the system in cancers.

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          Author and article information

          Journal
          Int J Cancer
          International journal of cancer
          Wiley
          0020-7136
          0020-7136
          Jul 03 1997
          : 72
          : 1
          Affiliations
          [1 ] Department of Molecular and Structural Biology, University of Aarhus, Denmark. pa@mbio.aau.dk
          Article
          10.1002/(SICI)1097-0215(19970703)72:1<1::AID-IJC1>3.0.CO;2-Z
          10.1002/(sici)1097-0215(19970703)72:1<1::aid-ijc1>3.0.co;2-z
          9212216
          a2856d7a-53e2-4fbd-b94c-8a9c09e17a5b
          History

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