Summary
Using batroxobin, a thrombin-like enzyme found in snake venom, the effects of defibrinogenation on artificial lung metastasis in mice were studied. The role of natural killer (NK) cells in the inhibitory effects of defibrinogenation on metastasis was also investigated. Artificial lung metastasis experiments were performed by inoculating either B16-F10 cells or B16-BL/6 cells, highly metastatic strains of B16 melanoma cells, into C57BL/6 mice via the tail vein. The administration of batroxobin significantly inhibited lung metastasis, as did NK activity augmented by poly (I) · poly (C) administration. When both batroxobin and poly (I) · poly (C) were administered, lung metastasis was more markedly inhibited. When NK activity was suppressed by administration of anti-(asialo GM1) antibody, lung metastasis was markedly increased. When batroxobin was administered with anti-(asialo GM1) antibody, no inhibitory effects on lung metastasis, such as those seen with batroxobin alone, were observed. The administration of batroxobin had no effect at all on spleen lymphocyte NK activity. These results indicated that defibrinogenation due to batroxobin inhibits lung metastasis, and these effects depend on NK activity of the host.
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Abbreviations
- NK:
-
natural killer
- BU:
-
batroxobin units
- FCS:
-
fetal calf serum
References
Ambrus J, Ambrus C, Gastpar H (1982) Platelet aggregation inhibitors and metastatic spread of neoplastic cells. Prog Clin Biol Res 89:83–96
Chmielewska J, Poggi A, Janic P, Latallo ZS, Danati MB (1980) Effect of defibrination with batroxobin on growth and metastasis of JW sarcoma in mice. Eur J Cancer 16:919–923
Collins JL, Patek PQ, Cohn M (1981) Tumorigenicity and lysis by natural killers. J Exp Med 153:89–106
Donati MB, Musoni L, Poggi A, De Gaetano G, Garattini S (1978) Growth and metastasis of the Lewis lung carcinoma in mice defibrinated with batroxobin. Eur J Cancer 14:343–349
Dvorak H, Senger D, Dvorak A (1983) Fibrin as a component of the tumor stoma: origins and biological significance. Cancer Metastasis Rev 2:41–73
Egberg N (1979) On the metabolism of the thrombin-like enzyme from the venom ofBothrops atrox. Thromb Res 4:35–53
Glaves D, Weiss L (1978) Initial tumor-cell arrest in animals of defined coagulative status. Int J Cancer 21:741–746
Gorelik E (1987) Augmentation of the antimetastatic effect of anticoagulant drugs by immunostimulation in mice. Cancer Res 47:809–815
Gorelik E, Wiltrout RH, Okumura K, Habu S, Herberman RB (1982) Role of NK cells in the control of metastatic spread and growth of tumor cells in mice. Int J Cancer 30:107–112
Gorelik E, Bere WW, Herberman RB (1984) Role of NK cells in the antimetastatic effect of anticoagulant drugs. Int J Cancer 33:87–94
Habu S, Fukumi H, Shimamura K, Kasai M, Nagai Y, Okumura K, Tamaoki N (1981) In vivo effects of anti-asialo GM1. I. Reduction on NK activity and enhancement of transplanted tumor growth in nude mice. J Immunol 127:34–38
Hanna N, Fidler IJ (1980) Role of natural killer cells in the destruction of circulating tumor emboli. J Natl Cancer Inst 65:801–809
Hilgard P (1982) Blood platelets and tumor dissemination. Prog Clin Biol Res 89:143–155
Ivarson L (1976) Pulmonary metastasis formation after intravenous tumor cell injection in defibrinogenated rats. Z Krebsforsch 85:83–90
Jones D, Wallace A, Fraser E (1971) Sequence of events in experimental metastases or Walker-256 tumor: light, immunofluorescent and electron microscopic observation. J Natl Cancer Inst 46:493–501
Kramer R, Nicolson G (1979) Interactions of tumor cells with vascular endothelial cell monolayers. A model for metastatic invasion. Proc Natl Acad Sci USA 76:5704–5708
Leloup P (1973) Observations sur la réproduction de Bothrop moojeni Hoge en captivité. Acta Zool Pathol Antverp 62:173–201
Prentice CRM, Edger E, McNicol GP (1974) Characterization of fibrin degradation products in patients on ancrod therapy: comparison with fibrinogen derivatives produced by plasmin. Br J Haematol 27:77–87
Riccardi C, Puccetti P, Santoni A, Herberman RB (1979) Rapid in vivo assay of mouse natural killer cell activity. J Natl Cancer Inst 63:1041–1045
Shibuya M, Saijo N, Ozaki A, Beppu Y, Shimizu E, Takizawa T, Hoshi A (1983) Role of asialo GM1 positive cells in the control of metastatic spread of tumor cells in mice. Jpn J Cancer Chemother 10:1781–1786
Siegel S (1956) Nonparametric Statistics for the behavioral science. McGraw-Hill, New York, pp 116–126
Sindelar W, Tralka T, Ketcham A (1975) Electron microscopic observation on formation of pulmonary metastases. J Surg Res 18:137–161
Stocker K (1978) Defibrinogenation with thrombin-like snake venom enzymes. In: Markwardt F (ed) Fibrinolytics and antifibrinolytics. Springer, Berlin Heidelberg New York, pp 451–484
Stocker K, Egberg N (1973) Reptilase as a defibrinogenation agent. Thromb Diath Haemorrh [Suppl] 54:361–370
Warren BA (1974) Tumor metastasis and thrombosis. Thromb Diath Haemorrh [Suppl] 59:139–156
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Shibuya, M., Niitani, H., Aoyama, A. et al. Antimetastatic effect of defibrinogenation with batroxobin depends on the natural killer activity of host in mice. J Cancer Res Clin Oncol 116, 168–172 (1990). https://doi.org/10.1007/BF01612672
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DOI: https://doi.org/10.1007/BF01612672