Growth and dissemination of Lewis lung carcinoma in plasminogen-deficient mice.
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.
Bugge
T H
TH
Divisions of Developmental Biology and Pathology, Children's Hospital Research Foundation, Cincinnati, OH, USA.
Kombrinck
K W
KW
Xiao
Q
Q
Holmbäck
K
K
Daugherty
C C
CC
Witte
D P
DP
Degen
J L
JL
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000401:mortality / Q000473:pathology*; D005341:Fibrinolysin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D009368:Neoplasm Transplantation; D010958:Plasminogen / Q000172:deficiency*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D010958:Plasminogen; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator