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

Abstract

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 plasminogendeficient (Pig-/-) mice and matched control mice. Primary tumors developed in all mice with no difference in the rate of appearance between Pig"/' and control mice. However, the primary tumors in Pig-/- mice were smaller, less hemorrhagic, and displayed reduced skin ulcération. In addition, dissemination of the tumor to regional lymph nodes was delayed in Pig-/- mice. Surprisingly, no quantitative differences were observed in lung metastasis between Pig-/- and control mice. Furthermore, Pig-deficiency was compatible with metastasis of the primary tumor to a variety of other organs. Nevertheless, Pig-/- mice displayed a moderately increased survival after primary tumor resection. These findings demonstrate that plasmin-mediated proteolysis contributes to the morbidity and mortality of Lewis lung carcinoma in mice, but sufficient proteolytic activity is generated in Pig-/- mice for efficient tumor development and metastasis.