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Reduced metastasis of Polyoma virus middle T antigen-induced mammary cancer in plasminogen-deficient mice

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • T H Bugge
  • L R Lund
  • K K Kombrinck
  • B S Nielsen
  • K Holmbäck
  • A F Drew
  • M J Flick
  • D P Witte
  • K Danø
  • J L Degen

To investigate the role of plasmin(ogen) in mammary tumor development and progression, plasminogen-deficient mice were crossed with transgenic mice expressing Polyoma middle T antigen under the control of the mouse mammary tumor virus long terminal repeat. Virgin females carrying the Polyoma middle T antigen uniformly developed multiple, bilateral mammary tumors, regardless of the presence or absence of circulating plasminogen. Both the age at which these tumors became palpable and subsequent tumor growth were indistinguishable between plasminogen-deficient mice and plasminogen-expressing littermates. However, plasminogen was found to greatly modify the metastatic potential in this model system; lung metastasis in plasminogen-deficient mice was significantly reduced as compared to littermate controls with respect to frequency of occurrence, total number of metastases, and total metastatic tumor burden. Plasminogen activators, as well as other key factors that govern the conversion of plasminogen to plasmin, were expressed within the mammary tumors, suggesting that the plasminogen/plasmin system may promote metastasis by contributing to tumor-associated extracellular proteolysis. The data provide direct evidence that plasmin(ogen) is a tumor progression factor in PymT-induced mammary cancer, and support the hypothesis that hemostatic factors play an important role in tumor biology.

OriginalsprogEngelsk
TidsskriftOncogene
Vol/bind16
Udgave nummer24
Sider (fra-til)3097-104
Antal sider8
ISSN0950-9232
DOI
StatusUdgivet - 18 jun. 1998

ID: 201190074