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Tumor cell-platelet interactions in vitro and their relationship to in vivo arrest of hematogenously circulating tumor cells

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Abstract

Aggregation of rat platelets was induced in vitro by homologous rat Walker 256 carcinosarcoma cells and the extent of tumor cell-platelet interactions examined ultrastructurally. By 30s there was surface contact between unstimulated platelets and tumor cell microvilli. By midphase aggregation (2–3 min) tumor cells became enmeshed within expanding platelet aggregates. Tumor cell microvilli and platelet pseudopodia interdigitated as aggregation progressed. During the later stages of aggregation (6–10 min) tumor cells formed large processes which penetrated deep into the aggregate. Platelet activation (i.e. degranulation) occurred in gradient fashion and was concentrated near tumor cell membrane sites involved in process formation. At these later stages tumor cells near the aggregate periphery were found to have engulfed platelets or platelet fragments.

Tumor cell-platelet interactions in the pulmonary microvasculature were also studied in vivo following injection of murine Lewis lung carcinoma, 16C mammary adenocarcinoma, and B16 amelanotic melanoma tumor cells into the tail vein. Platelets demonstrated a biphasic association with arrested tumor cells with peak interactions occurring at 10–30 min and 4–24h. Ultrastructurally, tumor cells exhibited newly formed processes which interdigitated with the platelet aggregate. Such processes formed only in areas of contact with platelets and not in areas of contact with endothelial cells or other blood elements (i.e. erythrocytes, polymorphonuclear leukocytes). Numerous tumor cell mitochondria were concentrated in the areas of greatest platelet-tumor cell process activity. At early time intervals (2–10 min), intravascular platelet degranulation was observed primarily in platelets associated with tumor cell processes. Tumor cells also were found to have engulfed platelet fragments in vivo.

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References

  1. Agostino, D., Grossi, C. E., and Clifton, E. E., 1961, The effect of human fibrinolysin on hepatic metastases in simulated colon carcinoma in rats. Annals of Surgery, 153, 365–368.

    Google Scholar 

  2. Bastida, E., Ordinas, A., Giardina, S. L., and Jamieson, G. A., 1982, Differentiation of platelet-aggregating effects of human tumor lines based on inhibition studies with apyrase, hirudin, and phospholipase. Cancer Research, 42, 4348–4352.

    Google Scholar 

  3. Braun, J., Fujiwara, K., Pollard, T. D., and Unanae, E. R., 1978, Two distinct mechanisms for redistribution of lymphocyte surface macromolecules I. Relationship to cytoplasmic myosin. Journal of Cell Biology, 79, 409–418.

    Google Scholar 

  4. Cavanaugh, P. G., Sloane, B. F., Bajkowski, A. S., Gasic, G. J., Gasic, T. B., and Honn, K. V., 1983, Involvement of cathepsin B-like cysteine proteinase in platelet aggregation induced by tumor cells and their shed membrane vesicles. Clinical and Experimental Metastasis, 1, 297–307.

    Google Scholar 

  5. Cavanaugh, P. G., Sloane, B. F., Bajkowski, A. S., Taylor, J. D., and Honn, K. V., 1985, Purification and characterization of platelet aggregating activity from tumor cells: copurification with procoagulent activity. Thrombosis Research, 37, 309–326.

    Google Scholar 

  6. Chew, E. C., Josephson, R. L., and Wallace, A. C., 1975, Morphologic aspects of the arrest of circulating cancer cells. Fundamental Aspects of Metastasis, edited by L. Weiss (Amsterdam: North-Holland), pp. 121–150.

    Google Scholar 

  7. Chew, E. C., and Wallace, A. C., 1976, Demonstration of fibrin in early stages of experimental metastasis. Cancer Research, 36, 1904–1909.

    Google Scholar 

  8. Crissman, J. D., Hatfield, J., Schaldenbrand, M., Sloane, B. F., and Honn, K. V., 1985, Arrest and extravasation of B16 amelanotic melanoma in murine lungs. A light and electron microscopic study. Laboratory Investigation, 53, 470–478.

    Google Scholar 

  9. Gasic, G. J., 1984, Role of plasma, platelets and endothelial cells in tumor metastasis. Cancer Metastasis Reviews, 3, 99–116.

    Google Scholar 

  10. Grossi, C. E., Agostino, D., and Clifton, E. E., 1960, The effect of human fibrinolysin on pulmonary metastases of Walker 256 carcinosarcoma. Cancer Research, 20, 605–609.

    Google Scholar 

  11. Honn, K. V., Menter, D. G., Onoda, J. M., Taylor, J. D., and Sloane, B. F., 1984, Role of prostacyclin as a natural deterrent to hematogenous tumor metastasis. Cancer Invasion and Metastasis: Biologic and Theraputic Aspects, edited by G. L. Nicolson and L. Milas (New York: Raven Press), pp. 361–368.

    Google Scholar 

  12. Honn, K. V., Onoda, J. M., Menter, D. G., Taylor, J. D., and Sloane, B. F., 1984, Prostacyclin/thromboxanes and tumor cell metastasis. Hemostatic Mechanisms and Metastasis, edited by K. V. Honn and B. F. Sloane (Boston: Martinus Nijhoff), pp. 266–278.

    Google Scholar 

  13. Honn, K. V., Onoda, J. M., Menter, D. M., Taylor, J. D., and Sloane, B. F., 1985, Prostacyclin in the control of tumor metastasis. Biological Protection with Prostaglandins, edited by M. M. Cohen (Boca Ratan: CRC Press, Inc.), pp. 91–110.

    Google Scholar 

  14. Jones, D. S., Wallace, A. C., and Frazer, E. E., 1971, Sequence of events in experimental metastases of Walker-256 tumor: light, immunofluorescent and electron microscopic observations. Journal of the National Cancer Institute, 46, 493–504.

    Google Scholar 

  15. Kaplan, K. L., Broekman, M. J., Chernoff, A., Lesnik, G. R., and Drillings, M., 1979, Platelet alpha granule proteins: Studies on release and subcellular localization. Blood, 53, 604–618.

    Google Scholar 

  16. Kawaguchi, Y., 1982, Ultrastructural study on the release reaction of platelets I. Acta pathologica japonica, 32, 961–980.

    Google Scholar 

  17. Kawaguchi, Y., 1982, Ultrastructural study on the release reaction of platelets II. Acta pathologica japonica, 32, 981–1002.

    Google Scholar 

  18. Kawaguchi, T., Kawaguchi, M., Dulski, K. M., and Nicolson, G. L., 1985, Cellular behavior of metastatic B16 melanoma in experimental blood-borne implantation and cerebral invasion. Invasion and Metastasis, 5, 16–30.

    Google Scholar 

  19. Kepner, N., and Lipton, A., 1981, A mitogenic factor for transformed fibroblasts from human platelets. Cancer Research, 41, 430–432.

    Google Scholar 

  20. Kohler, N., and Lipton, A., 1971, Platelets as a source of fibroblast growth promoting activity. Experimental Cell Research, 87, 297–301.

    Google Scholar 

  21. Menter, D. G., Onoda, J. M., Taylor, J. D., and Honn, K. V., 1984, Effects of prostacyclin on tumor cell induced platelet aggregation. Cancer Research, 44, 450–456.

    Google Scholar 

  22. Ross, R., Glomset, J., Karinya, B., and Harker, L., 1974, A platelet dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proceedings of the National Academy of Sciences, U.S.A., 71, 1207–1210.

    Google Scholar 

  23. Ross, R., and Vogel, A., 1978, The platelet derived growth factor. Cell, 14, 203–210.

    Google Scholar 

  24. Ryan, R. E., Crissman, J. E., Honn, K. V., and Sloane, B. F., 1985, Cathepsin B-like activity in viable tumor cells isolated from rodent tumors. Cancer Research, 45, 3636–3641.

    Google Scholar 

  25. Sloane, B. F., Dunn, J. R., and Honk, K. V., 1981, Lysosomal cathepsin B: correlation with metastatic potential. Science, 212, 1151–1153.

    Google Scholar 

  26. Tohgo, A., Tanaka, N. G., and Ogawa, H., 1985, Platelet aggregating activities of metastasizing tumor cells. Invasion and Metastasis, 5, 96–105.

    Google Scholar 

  27. Turner, W. A., Szlag, D. C., and Taylor, J. D., 1985, Platelet fibronectin release induced by Walker 256 rat carcinosarcoma tumor cells. Clinical and Experimental Metastasis, 3, 209–220.

    Google Scholar 

  28. Warren, S., and Gates, O., 1936, The fate of intravenously injected tumor cells. American Journal of Cancer, 27, 485–492.

    Google Scholar 

  29. Warren, B. A., and Vales, O., 1972, The adhesion of thromboplastic tumor emboli to vessel walls in vivo. British Journal of Experimental Pathology, 53, 301–313.

    Google Scholar 

  30. Weiss, L., 1980, Cancer cell traffic from the lungs to the liver: an example of metastatic inefficiency. International Journal of Cancer, 25, 385–392.

    Google Scholar 

  31. Zeidman, I., and Buss, J. M., 1952, Transpulmonary passage of tumor cell emboli. Cancer Research, 12, 731–733.

    Google Scholar 

  32. Zeidman, I., 1957, Metastasis: a review of recent advances. Cancer Research, 17, 157–162.

    Google Scholar 

  33. Zucker, M. B., and Nachmias, V. T., 1985, Platelet activation. Arteriosclerosis, 5, 2–18.

    Google Scholar 

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Author notes

  1. David G. Menter

    Present address: Department of Tumor Biology, M. D. Anderson Hospital & Tumor Institute, Texas Medical Center, 77030, Houston, Texas, U.S.A.

Authors and Affiliations

  1. Department of Biological Sciences, Wayne State University, Harper-Grace Hospitals, and the Gershenson Radiation Oncology Center, 48202, Detroit, Michigan, U.S.A.

    David G. Menter, Carmel Harkins, John D. Taylor & Kenneth V. Honn

  2. Department of Radiation Oncology, Wayne State University, Harper-Grace Hospitals, and the Gershenson Radiation Oncology Center, 48202, Detroit, Michigan, U.S.A.

    David G. Menter, Bonnie F. Sloane, John D. Taylor & Kenneth V. Honn

  3. Department of Pathology, Wayne State University, Harper-Grace Hospitals, and the Gershenson Radiation Oncology Center, 48202, Detroit, Michigan, U.S.A.

    James S. Hatfield & John Crissman Crissman

  4. Department of Pharmacology, Wayne State University, Harper-Grace Hospitals, and the Gershenson Radiation Oncology Center, 48202, Detroit, Michigan, U.S.A.

    Bonnie F. Sloane

Authors
  1. David G. Menter
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  2. James S. Hatfield
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  5. John D. Taylor
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  6. John Crissman Crissman
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  7. Kenneth V. Honn
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Menter, D.G., Hatfield, J.S., Harkins, C. et al. Tumor cell-platelet interactions in vitro and their relationship to in vivo arrest of hematogenously circulating tumor cells. Clin Exp Metast 5, 65–78 (1987). https://doi.org/10.1007/BF00116627

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  • DOI: https://doi.org/10.1007/BF00116627

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