Maximum effect of urokinase plasminogen activator inhibitors in the control of invasion and metastasis of rat mammary cancer.

Experimentally induced pulmonary metastases of mammary cancer in the Fisher 344 rat can be suppressed by the inhibition of urokinase plasminogen activator (uPA). The inhibition of uPA with amiloride or B428 has been shown to be dose dependent. Increased dosage levels of inhibitors might be expected to enhance levels of suppression of metastases. The use of each of these inhibitors at equipotent concentrations that exceeded the doses administered in previous studies failed to eliminate pulmonary metastases. These results demonstrate that a maximum limit is attained for the inhibitory capacities on cells during in vitro invasion or in vivo metastasis. At increased levels, uPA inhibitors continue to suppress, but do not eradicate, experimental pulmonary metastases of MATB cell rat mammary cancer.