Studies on mechanisms involved in metastasis formation from circulating tumor cells

Factors influencing tumor cell lodgement during normal and post-traumatic conditions
  • G. Skolnik
  • M. Alpsten
  • L. Ivarsson
Original Papers Experimental Oncology

Summary

As shown in earlier studies the formation of metastases after i. v. tumor cell injection in rats is increased in the immediate post-traumatic period and treatment with heparin, thrombocytopenia, and defibrinogenation decreases the formation of metastases. Thrombocytopenia also inhibits the stimulating effect of trauma on metastasis formation. The results of the studies reported in this paper show that the changes of metastasis formation induced by the factors mentioned above with few exceptions are well correlated to the lodgement of the injected tumor cells. Thus, heparin treatment and thrombocytopenia decrease the pulmonary lodgement of i.v. injected tumor cells. Trauma increases the pulmonary lodgement of i.v. injected tumor cells but when trauma is combined with thrombocytopenia, the effect of thrombocytopenia dominates and the pulmonary lodgement of tumor cells decreases when compared to control conditions. Despite this, trauma still gives rise to increased tumor cell lodgement during thrombocytopenia.

Key words

Lodgement of tumor cells Heparin Thrombocytopenia Defibrinogenation Trauma 

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References

  1. Agostino D, Cliffton EE (1965) Trauma as a cause opf localization of blood-borne metastases: Preventive effect of heparin and fibrinolysis. Ann Surg 161:97–102Google Scholar
  2. Bergentz SE, Nilsson IM (1961) Effect of trauma on coagulation and fibrinolysis in dogs. Acta Chir Scand 122:21–29Google Scholar
  3. Born GVR (1962) Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature (Lond) 194:927–932Google Scholar
  4. Cronberg S (1968) Effect of fibrinolysis on adhesion and aggregation of human platelets. Thromb Diath Haemorrh 19:474–482Google Scholar
  5. Eika C (1971) Inhibition of thrombin induced aggregation of human platelets by heparin. Scand J Haematol 8:216–222Google Scholar
  6. Fisher B, Fisher ER (1959) Experimental studies of factors influencing hepatic metastases III. Effect of surgical trauma with special reference to liver injury. Ann Surg 150:731–744Google Scholar
  7. Fisher B, Fisher ER (Feduzka N (1967) Trauma and the localization of tumour cells. Cancer 20: 23–30Google Scholar
  8. Gaarder A, Jonsen J, Laland S, Hellem AJ, Owren PA (1961) Adenosine diphosphate in red cells as a factor in the adhesiveness of human blood platelets. Nature (Lond) 192:531–535Google Scholar
  9. Gasic JG, Gasic TB, Galanti N, Johnson T, Murphy S (1973) Platelet-tumor cell interaction in mice. The role of platelets in the spread of malignant disease. Int J Cancer 11:704–717Google Scholar
  10. Gelin L-E, Rudenstam C-M (1966) Trauma, microcirculation, and tumour spread. Swed Cancer Soc Yb 4:53–65Google Scholar
  11. Hilgard P (1973) The role of blood platelets in experimental metastases. Br J Cancer 28:429–435Google Scholar
  12. Honour AJ, Ross-Russel RW (1962) Experimental platelet embolism. Br J Exp Pathol 43:350–357Google Scholar
  13. Hovig T (1963) Aggregation of rabbit blood platelets produced in vitro by saline “extract” of tendons. Thromb Diath Haemorrh 9:248–263Google Scholar
  14. Hugues J, Lapiere CM (1964) Nouvelles recherches sur l'accolment des plaquettes aux fibres de collagene. Thromb Diath Haemorrh 11:327–334Google Scholar
  15. Ivarsson L, Rudenstam C-M (1975) Heparin, Dextran 1000, and metastasis formation after intravenous tumour cell injection in dextran non-sensitive rats. Br J Cancer 32:502–508Google Scholar
  16. Ivarsson L (1976a) Metastasis formation after intravenous tumour cell injection in thrombocytopenic rats. Eur Surg Res 8:51–60Google Scholar
  17. Ivarsson L (1976b) Pulmonary metastasis formation after intravenous tumour cell injection in defibrinogenated rats. Z Krebsforsch 85:83–90Google Scholar
  18. Ivarsson L (1976c) Pulmonary metastasis formation after trauma. An experimental study on the relevance of rheological disturbances of blood. Acta Chir Scand [Suppl] 463:Google Scholar
  19. Jerushalmy Z, Zucker MB (1966) Some effects of fibrinogen degradation products (FDP) on blood platelets. Thromb Diath Haemorrh 15:413–419Google Scholar
  20. Jones DS, Wallace AC, Fraser EE (1971) Sequence of events in experimental metastases of Walker 256 tumor. Light, immunofluorescent and electron microscopic observations. J. Nat Cancer Inst 46:293–498Google Scholar
  21. Ljungquist U, Leandoer L, Bergentz SE (1968) Immediate changes in the platelet adhesiveness after haemorrhage and induced coagulation. Bull Soc Int Chir 1:29–35Google Scholar
  22. Kowalski E, Kopex M, Wegrzynovicz Z (1964) Influence of fibrinogen degradation products (FDP) on platelet aggregation, adhesiveness, and viscous metamorphosis. Thromb Diath Haemorrh 10:406–423Google Scholar
  23. Lutz BR, Fulton GP, Akers RP (1951) White thromboembolism in the hamster cheek pouch after trauma, infection, and neoplasia. Circulation 3:329–335Google Scholar
  24. Mustard JF, Packam MA (1969) Platelet function and myocardial infarction. Circulation 40:[Suppl.4] 40Google Scholar
  25. O'Brien JR, Shoobridge SM, Finch W (1969) Comparison of the effect of heparin and citrate on platelet aggregation. J Clin Pathol 22:28–33Google Scholar
  26. Rudenstam C-M (1968) Experimental studies on trauma and metastasis formation. Acta Chir Scand [Suppl] 391:Google Scholar
  27. Skolnik G, Alpsten M, Ivarsson L (1980) The influence of trauma, Dextran 1000, and Dextran 40 on the lodgement of circulating tumour cells. Cancer Res Clin Oncol 97:241–248Google Scholar
  28. Warren BA, Vales O (1972) The adhesion of thromboplastic tumour emboli to vessel walls in vivo. Br J Cancer 53:301–322Google Scholar
  29. Wood Jr, S (1958) Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. AMA Arch Pathol 66:550–569Google Scholar
  30. Wood Jr S, Holyoke ED, Yardley JH (1961) Mechanisms of metastasis production by blood-borne cancer cells. Proc. 4th Can Cancer Conf. Academic Press, New York, pp 167–223Google Scholar
  31. Zucker MB, Borelli J (1962) Platelet clumping produced by connective tissue suspensions and by collagen. Proc Soc Exp Biol Med 109:779–787Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • G. Skolnik
    • 1
    • 2
  • M. Alpsten
    • 1
    • 2
  • L. Ivarsson
    • 1
    • 2
  1. 1.Department of Surgery IUniversity of GöteborgGöteborgSweden
  2. 2.Radiation Physics Department, Sahlgrenska SjukhusetUniversity of GöteborgGöteborgSweden

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