Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

The effect of thrombocytopenia and antiserotonin treatment on the lodgement of circulating tumor cells

A vital fluorescence microscopic, electron microscopic and isotope study in the rat

  • 20 Accesses

  • 28 Citations

Summary

The hepatic lodgement of intraportally injected fibrosarcoma cells was analysed with a combination of vital fluorescence microscopic, electron microscopic and isotope techniques in normal, thrombocytopenic and antiserotonin treated (Ketanserin) rats. Ketanserin had no effect on the initial arrest of the tumor cells, as measured 5 min after tumor cell injection, which is in analogy with our previous results on thrombocytopenia. Three hours after injection, the number of lodged tumor cells was significantly reduced by both thrombocytopenia and Ketanserin treatment. Thrombocytopenia was more efficient in reducing tumor cell lodgement than antiserotonin treatment. The in vivo and electron microscopic observations indicated that the reduction of tumor cell lodgement was due to an increased destruction of tumor cells. The similar effects of Ketanserin and thrombocytopenia suggest that serotonin, when released from platelets activated in the presence of tumor cells, increases the survival of fibrosarcoma cells lodged in the liver.

This is a preview of subscription content, log in to check access.

References

  1. Bagge U, Skolnik G, Ericson LE (1983) The arrest of circulating tumour cells in the liver microcirculation. A vital fluorescence microscopic, electron microscopic and isotope study in the rat. J Cancer Res Clin Oncol 105: (in press)

  2. Baumgartner HR (1969) 5-hydroxytryptamine uptake and release in relation to aggregation of rabbit platelets. J Physiol 201:409–423

  3. Boeryd B (1965) Action of heparin and plasminogen inhibitor (EA-CA) on metastatic tumor spread in an isologous system. Acta Pathol Microbiol Scand 65:395–404

  4. Boucek RJ, Alvarez TR (1971) Increase in survival of subcultured fibroblasts mediated by serotonin. Nature New Biol 229:61–62

  5. Chew EC, Josephsson RL, Wallace AC (1976) Morphologic aspects of the arrest of circulating cancer cells. In: Weiss L (ed) Fundamental aspects of metastasis. North Holland, Amsterdam, p 121–150

  6. Clark RA, Szot S (1981) The myeloperoxidase-hydrogen peroxidehalide system as effector of neutrophil-mediated tumour cell cytotoxicity. J Immunol 126:1295–1301

  7. De Clerck F (1979) The effect of oral administration of R41468 to human volunteers on the ex vivo platelet aggregation induced or potentiated by serotonin. Clinical Research Report on R41468 No. 11. Janssen Pharmaceutica, Beerse, Belgium

  8. Csaba G, Lantos T (1973) Effect of hormones on protozoa. Studies on the phagocytotic effect of histamine, 5-hydroxytryptamine and indolacetic acid in Tetrahymena pyriformis. Cytobiology 7:361–365

  9. Fidler IJ (1970) Metastasis: Quantitative analysis of distribution and fate of tumour emboli labelled with 125I-5-iodo-2-deoxyuridine. J Nat Cancer Inst 45:773–782

  10. Gasic GJ, Gasic TB, Stewart CC (1968) Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci USA 61:46–52

  11. Gasic GJ, Gasic TB, Galanti N, Johnson T, Murphy S (1973) Platelet-tumour cell interactions in mice. The role of platelets in the spread of malignant disease. Int J Cancer 11:704–718

  12. Gasic GJ, Koch PAG, Hsu B, Gasic TB, Niewiarowski S (1976) Thrombogenic activity of mouse and human tumours: Effects on platelets, coagulation and fibrinolysis and possible significance for metastases. Z Krebsforsch 86:263–277

  13. Haddy FJ, Scott JB, Grega GJ (1976) Peripheral circulation: fluid transfer across the microvascular membrane. In: Guyton AC, Cowley AW (eds) International review of physiology II, vol 9. University Park Press, Baltimore London Tokyo pp 63–109

  14. Hagmar B, Boeryd B (1969) Disseminating effect of heparin on experimental tumour metastases. Pathol Eur 4:274–282

  15. Hilgard P, Heller H, Schmidt CG (1976) The influence of platelet aggregation inhibitors on metatasis formation in mice. Z Krebsforsch 86:243–250

  16. Ivarsson L, Rudenstam CM (1975) Dextrans and the formation of pulmonary metastases after intravenous tumour cell injection in dextran non-sensitive rats. Eur Surg Res 7:326–340

  17. Ivarsson L (1976a) Pulmonary metastasis formation after trauma. Acta Chir Scand (Suppl 463) Dissertation, University of Göteborg, Göteborg, Sweden

  18. Ivarsson L (1976b) Metastasis formation after intravenous tumor cell injection in thrombocytopenic rats. Eur Surg Res 8:51–60

  19. Jones DS, Wallace AC, Fraser EE (1971) Sequence of events in experimental metastases of Walker 256 tumour: light, immunofluorescent and electron microscopic observations. J Natl Cancer Inst 46:493–504

  20. Jong EC, Klebanoff SJ (1980) Eosinophil-mediated mammalian tumour cell cytotoxicity, role of the peroxidase system. J Immunol 124:1949–1953

  21. Kaltenbach JP, Kaltenbach MH, Lyons WB (1958) Nigrosin as a dye for differentiating live and dead ascites cells. Exp Cell Res 15:112

  22. Leysen JE, Awcuters F, Kennis L, Laduron PM, Vanderberk J, Janssen PAJ (1981) Receptor binding profile of R41468, a novel antagonist at 5-HT2 receptors. Life Sci 28:1115–1122

  23. Maat B (1978) Extrapulmonary colony formation after intravenous injection of tumour cells into heparin-treated animals. Br J Cancer 37:369–376

  24. Mills DCB, Robb IA, Roberts GCK (1968) The release of nucleotides, 5-hydroxytryptamine and enzymes from human blood platelets during aggregation. J Physiol 195:715–729

  25. Roos E, Dingemans KP, van de Pavert IV, van der Berg-Weerman MA (1978) Mammary carcinoma cells in mouse liver: infiltration of liver tissue and interaction with Kupffer cells. Br J Cancer 38:88–99

  26. Sindelar WF, Tralka TS, Ketcham AS (1975) Electron-microscopic observations of formation of pulmonary metastases. J Surg Res 18:137–161

  27. Skolnik G, Alpsten M, Ivarsson L (1980a) The influence of trauma, dextran 100 and dextran 40 on the ldogement of circulating tumour cells. J Cancer Res Clin Oncol 97:241–248

  28. Skolnik G, Alpsten M, Ivarsson L (1980b) Studies on mechanisms involved in metastasis formation from circulating tumour cells. Factors influencing tumour cell lodgement during normal and post-traumatic conditions. J Cancer Res Clin Oncol 97:249–256

  29. Skolnik G, Bagge U, Ericson LE (1981) Vital- and electron microskopic observations of tumour cell lodgement in the liver. World J Surg 5:442

  30. Sugerbaker EV, Ketcham AS (1977) Mechanisms and prevention of cancer dissemination: an overview. Semin Oncol 4:19–32

  31. Warren BA, Vales O (1972) The adhesion of thromboplastic tumour emobli to vessel walls in vivo. Br J Exp Pathol 53:301–313

  32. Wood Jr S (1958) Pathogenesis of metastasis formation oberved in vivo in the rabbit ear chamber. AMA Arch Pathol 66:550–568

  33. Wood Jr S, Holyoke D, Yardley JM (1961) mechanisms of metastasis production by blood-borne cancer cells. Can Cancer Conf 4:167–223

  34. Wood Jr S, Hilgard P (1972) Aspirin and tumour metastasis. Lancet 2:1416

Download references

Author information

Correspondence to U. Bagge.

Additional information

Supported by grants from the Göteborg Medical Society, the Medical Faculty, University of Göteborg and the Swedish Medical Research Council (12X-00663)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Skolnik, G., Ericson, L.E. & Bagge, U. The effect of thrombocytopenia and antiserotonin treatment on the lodgement of circulating tumor cells. J Cancer Res Clin Oncol 105, 30–37 (1983). https://doi.org/10.1007/BF00391829

Download citation

Key words

  • Tumor cell lodgement
  • Thrombocytopenia
  • Antiserotonin treatment
  • Phagocytosis of tumor cells