GROWTH AND DISSEMINATION OF LEWIS LUNG-CARCINOMA IN PLASMINOGEN-DEFICIENT MICE

Plasminogen activation has been proposed to play a critical role in ca ncer invasion and metastasis. The effects of complete ablation of plas minogen activation in cancer was studied by inoculation of a metastati c 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 tu mors in Plg(-/-) mice were smaller and less hemorrhagic and displayed reduced skin ulceration. In addition, dissemination of the tumor to re gional lymph nodes was delayed in Plg(-/-) mice. Surprisingly, no quan titative differences were observed in lung metastasis between Plg(-/-) and control mice. In addition, Pig deficiency was compatible with met astasis of the primary tumor to a variety of other organs. Nevertheles s, Plg(-/-) mice displayed a moderately increased survival after prima ry tumor resection. These findings suggest that plasmin-mediated prote olysis contributes to the morbidity and mortality of Lewis lung carcin oma in mice, but sufficient proteolytic activity is generated in Plg(- /-) mice for efficient tumor development and metastasis. (C) 1997 by T he American Society of Hematology.