We studied the effects of the
plasminogen activator inhibitor-1 (PAI-1), the
urokinase-type plasminogen activator (uPA) and their
antibodies on hematogeneous pulmonary
metastases formation of human
fibrosarcoma in athymic mice. We used a human
fibrosarcoma cell line (HT-1 080) with low metastatic potential, and a subpopulation of HT-1 080 (HT-1 080-P4) with high metastatic potential which was selected by repeating
injections into the tail veins of athymic mice. We examined the effects of these drugs on pulmonary
metastases formation according to Wexler's method and the number of
tumor cell emboli in the lung subsequent to an injection of radio-labeled
tumor cells. Pulmonary
metastases formation from HT-1 080 was not affected by any of the tested drugs. Pulmonary
metastases from HT-1 080-P4 increased with uPA and anti-uPA antibody
injections.
PAI-1 slightly increased pulmonary
metastases from HT-1 080-P4, and the anti-PAI-1 antibody decreased it (60.9 + 27.7% of control, p < 0.05). While none of the drugs altered the number of HT-1 080 cells in the lung at 24, 48 and 72 hours after the injection,
PAI-1 increased the number of HT-1 080-P4 cells in the lung, whereas uPA and
PAI-1 decreased it. The result that these drugs did not affect the metastatic potential of HT-1 080 but only that of HT-1 080-P4, indicates that fibrinolysis plays an important role in hematogenous pulmonary
metastases formation of
tumor cells with high metastatic potential. The effects of uPA suggest that uPA facilitates pulmonary
metastasis formation probably due to an increase in the invasive ability of
tumor cells. The effects of
PAI-1 and its antibody of HT-1 080-P4 cells suggest that
PAI-1 may facilitate
tumor cell lodgement in vessels and the anti-PAI-1 antibody could be able to suppress pulmonary
metastases of
tumor cells with high metastatic potential by inhibition of
tumor cell lodgement in vessels.