Streptokinase inhibits pulmonary tumor seeding in an animal experimental model.
One aspect of the metastatic process involves entrapment of tumor cells within the microcirculation of organs in a "fibrin-platelet mesh." We postulate that destruction of this mesh by fibrinolysis might discourage tumor seeding, thereby inhibiting metastasis. To study this hypothesis, the effect of intravenous streptokinase on pulmonary tumor seeding was examined in a rodent model. In vitro experiments demonstrated that streptokinase had no cytotoxic or cytostatic effect on the Mtln3 cell line. Pharmacokinetic studies showed that at 30,000 U/kg, streptokinase caused systemic fibrinolysis in the Fischer rat, as demonstrated by the thrombin time and fibrin plate lysis assay. Streptokinase administered at this dose, 30 min after tumor cell injection, caused a significant decrease in pulmonary tumor seeding (median 23.0 in the streptokinase-treated group vs. 67.5 in untreated controls, P < 0.0001, Mann-Whitney U-test). Analysis of fibrin degradation products in the streptokinase-treated group suggested that this effect might be secondary to fibrinolysis. The implications of these findings are discussed.
Purushotham
A D
AD
University Department of Surgery, Western Infirmary, Glasgow, Scotland.
Brown
D C
DC
McCulloch
P
P
Choy
A
A
George
W D
WD
D000230:Adenocarcinoma / Q000556:secondary; D000818:Animals; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000187:drug effects; D008175:Lung Neoplasms / Q000097:blood / Q000517:prevention & control*; D009366:Neoplasm Seeding; D051381:Rats; D011916:Rats, Inbred F344; D013300:Streptokinase / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D005338:Fibrin Fibrinogen Degradation Products; D013300:Streptokinase