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Growth and dissemination of Lewis lung carcinoma in plasminogen-deficient mice

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • T H Bugge
  • K W Kombrinck
  • Q Xiao
  • K Holmbäck
  • C C Daugherty
  • D P Witte
  • J L Degen

Plasminogen activation has been proposed to play a critical role in cancer invasion and metastasis. The effects of complete ablation of plasminogen activation in cancer was studied by inoculation of a metastatic Lewis lung carcinoma expressing high levels of plasminogen activator into plasminogen-deficient (Plg-/-) mice and matched control mice. Primary tumors developed in all mice with no difference in the rate of appearance between Plg-/- and control mice. However, the primary tumors in Plg-/- mice were smaller and less hemorrhagic and displayed reduced skin ulceration. In addition, dissemination of the tumor to regional lymph nodes was delayed in Plg-/- mice. Surprisingly, no quantitative differences were observed in lung metastasis between Plg-/- and control mice. In addition, Plg deficiency was compatible with metastasis of the primary tumor to a variety of other organs. Nevertheless, Plg-/- mice displayed a moderately increased survival after primary tumor resection. These findings suggest that plasmin-mediated proteolysis contributes to the morbidity and mortality of Lewis lung carcinoma in mice, but sufficient proteolytic activity is generated in Plg-/- mice for efficient tumor development and metastasis.

OriginalsprogEngelsk
TidsskriftBlood
Vol/bind90
Udgave nummer11
Sider (fra-til)4522-31
Antal sider10
ISSN0006-4971
StatusUdgivet - 1 dec. 1997

ID: 201190164