Promotion of lung tumor colonization in mice by the synthetic thrombin inhibitor (no. 805) and its reversal by leech salivary gland extracts.
The role of anticoagulation per se in the reduction of experimental or spontaneous metastasis still remains to be determined, as shown by the conflicting results reported by the literature using different conventional anticoagulants. A new compound has been synthesized (compound no. 805) which prolongs or suppresses coagulation via specific inhibition of thrombin and its possible use in a model of experimental metastasis to clarify the role of anticoagulants in tumor spread was investigated. Contrary to our expectations, this compound increased rather than decreased the number of lung colonies induced by intravenous injections of a variety of murine neoplasias. Studies of the mechanism of this effect indicated that the compound increases retention of tumor cells by the lung without apparent impairment of the natural cell immune system, suggesting that the synthetic thrombin inhibitor may enhance vascular attachment of tumor cells. The promoting effect of compound no. 805 on metastasis was totally reversed by the administration of leech salivary gland extracts, which appear to protect capillaries from damage produced by cyclophosphamide, as revealed by other studies.
D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D002277:Carcinoma / Q000556:secondary; D005260:Female; D007865:Leeches; D008175:Lung Neoplasms / Q000556:secondary*; D008264:Macrophages / Q000187:drug effects; D008545:Melanoma / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010587:Phagocytosis / Q000187:drug effects; D010875:Pipecolic Acids / Q000494:pharmacology*; D012469:Salivary Glands / Q000502:physiology*; D012513:Sarcoma, Experimental / Q000556:secondary; D013154:Spleen / Q000187:drug effects; D013449:Sulfonamides; D013918:Thrombin Time
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban