The antibody to plasminogen activator inhibitor-1 suppresses pulmonary metastases of human fibrosarcoma in athymic mice.
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.
Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Japan.
H
H
Tsuchiya
S
S
Katsuo
E
E
Matsuda
C
C
Sunayama
K
K
Tomita
Y
Y
Ueda
B R
BR
Binder
D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology / Q000556:secondary*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology
D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator