Skip to main content

Advertisement

Log in

Effects of RA 233 treatment on the adhesive, invasive and metastatic properties of 13762NF rat mammary tumor cells

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

The pyrimido-pyrimidine analogue RA 233 has pleiotropic and differential effects on cultured tumor cell clones isolated from the 13762NF rat mammary adenocarcinoma. A nonresponsive clone of low metastatic potential (MTC) was not modified in its cell fragility or invasive, adhesive or lung-colonizing properties by RA 233 treatment. In contrast, a drug-responsive clone of high metastatic potential (MTLn3) was rendered less invasive and its cell fragility was decreased with RA 233 treatment, although its adhesiveness to lung microvascular endothelial cells and subendothelial matrix was unaffected by RA 233. Lung colonization of intravenously injected MTLn3 cells in syngeneic rats was significantly increased by RA 233 treatment, whereas spontaneous metastasis from the mammary fat pad to lung sites was decreased, although this decrease was not statistically significant.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ambrus, J. L., Ambrus, C. M., Gastpar, H., Huberman, E., Montagna, R., Biddle, W., Leong, S., andHoroszewicz, J., 1982,Interaction of Platelets and Tumor Cells.Progress in Clinical and Biological Research (New York: Alan R. Liss, Inc.), pp. 97–108.

    Google Scholar 

  2. Ambrus, J. L., Ambrus, C. M., andGastpar, H., 1978, Studies on platelet aggregationin vivo. VI. Effect of pyrimido-pyrimidine derivative (RA 233) on tumor cell metastasis.Journal of Medicine,9, 183–186.

    PubMed  Google Scholar 

  3. Belloni, P. N., andNicolson, G. L., 1988, Differential expression of cell surface glycoproteins on organ-derived murine vascular endothelia and endothelial cells.Journal of Cellular Physiology, in press.

  4. Biddle, W., Montagna, R. A., Leong, S. S., Horoszewics, J., Gastpar, H., andAmbrus, J. L., 1984, Antineoplastic effect of the pyrimido-pyrimidine derivative: RA 233.Pathology and Biology,32, 9–13.

    Google Scholar 

  5. Cucuianu, M. P., Nishizawa, E. E., andMustard, J. F., 1971, Effect of pyrimido-pyrimidine compounds on platelet function.Journal of Laboratory Medicine,77, 958–974.

    Google Scholar 

  6. Donati, M. B., Poggi, A., Mussoni, A., Degaetano, G., andGarattini, S., 1977,Cancer Invasion and Metastasis: Biological Mechanisms and Therapy (New York: Raven Press), pp. 151–160.

    Google Scholar 

  7. Erkell, L. J., andSchirrmacher, V., 1988, A quantitativein vitro assay for tumor cell invasion through extracellular matrix (ECM) or into protein gels.Cancer Research (In press).

  8. Gabor, H., andWeiss, L., 1986, Perturbations in cancer cell deformability and resistance to shear forces.Invasion and Metastasis,6, 166–179.

    Google Scholar 

  9. Gardner, R. V., Tebbi, C. K., andAmbrus, J. L., 1980, The comparison ofin vitro andin vivo effects of phosphodiesterase inhibitors-prostaglandin I2 releasers on granulopoiesis.Journal of Medicine,11, 361–376.

    PubMed  Google Scholar 

  10. Gasic, G. J., Gasic, T. B., Galanti, N., Johnson, T., andMurphy, S., 1973, Platelettumor cell interactions in mice. The role of platelets in the spread of malignant disease.International Journal of Cancer,11, 704–718.

    Google Scholar 

  11. Gastpar, H., Ambrus, J. L., andAmbrus, C. M., 1982,Interaction of Platelets and Tumor Cells.Progress in Clinical and Biological Research (New York: Alan R. Liss, Inc.), pp. 63–82.

    Google Scholar 

  12. Hart, I. R., Raz, A., andFidler, I. J., 1980, Effect of cytoskeleton-disrupting agents on the metastatic behavior of melanoma cells.Journal of the National Cancer Institute,64, 891–899.

    PubMed  Google Scholar 

  13. Hassanein, A. A., Turpie, A. G. G., McNicol, G., andDouglas, A. S., 1970, Effect of RA 233 on platelet functionin vitro.British Medical Journal,2, 83–86.

    PubMed  Google Scholar 

  14. Hilgard, P., Heller, H., andSchmidt, C. G., 1976, The influence of platelet aggregation inhibitors on metastasis formation in mice (3LL).Zeitschrift für Krebsforschung und Klinische Onkologie,86, 243–250.

    Google Scholar 

  15. Honn, K. V., 1983, Inhibition of tumor cell metastasis by modulation of the vascular prostacyclin/thromboxane A2 system.Clinical and Experimental Metastasis,1, 103–114.

    PubMed  Google Scholar 

  16. Irimura, T., Gonzalez, R., andNicolson, G. L., 1981, Effects of tunicamycin on B16 metastatic melanoma cell surface glycoproteins and blood-borne arrest and survival properties.Cancer Research,41, 3411–3418.

    PubMed  Google Scholar 

  17. Iwamoto, Y., Robey, F. A., Graf, J., Sasaki, M., Kleinman, H. K., Yamada, Y., andMartin, G. R., 1987, YIGSR, a synthetic laminin penta peptide, inhibits experimental metastasis formation.Science,238, 1132–1134.

    PubMed  Google Scholar 

  18. Li, X.-T., andHellmann, K., 1983, Effect of RA 233 alone and combined with radiation on experimental tumour metastasis.Clinical and Experimental Metastasis,1, 51–59.

    PubMed  Google Scholar 

  19. Li, X.-T., andHellmann, K., 1983, Antitumor effect of RA 233 alone and combined with radiotherapy.Clinical and Experimental Metastasis,1, 181–190.

    PubMed  Google Scholar 

  20. Lichtner, R. B.,Gallick, G. E., andNicolson, G. L., 1988, Modulation of the growth-promoting activity of EGF in cultured 13762NF rat mammary adenocarcinoma cells by RA 233.Journal of Cellular Physiology, in press.

  21. Lichtner, R. B., Goka, T. J., Butcher, R. W., andNicolson, G. L., 1987, Direct effects of the pyrimido-pyrimidine derivative RA 233 (Rapenton) on rat 13762NF mammary tumor cell clonesin vitro.Cancer Research,47, 1870–1877.

    PubMed  Google Scholar 

  22. Lichtner, R. B., andHaarmann, K., 1982,Interactions of Platelets and Tumor Cells: Progress in Clinical and Biological Research (NewYork: Alan R. Liss, Inc.), pp. 131–141.

    Google Scholar 

  23. Lichtner, R. B., Hutchinson, G., andHellmann, K., 1985, Antiplatelet pyrimido-pyrimidines and metastasis.Cancer Treatment Reviews,12, 221–234.

    PubMed  Google Scholar 

  24. Lichtner, R. B., andNicoloson, G. L., 1987, Effects of the pyrimido-pyrimidine derivative RX-RA 85 on metastatic tumor cell-vascular endothelial cell interactions.Clinical and Experimental Metastasis,5, 219–231.

    PubMed  Google Scholar 

  25. Lichtner, R. B., andNicolson, G. L., 1987, Effects of the pyrimido-pyrimidine derivatives RA 233 and RX-RA 85 on the growth and cytoskeletal organization of rat mammary adenocarcinoma cells.European Journal of Cancer and Clinical Oncology,23, 1269–1275.

    Google Scholar 

  26. Lichtner, R. B., andWedderburn, N., 1984, Enhancement of the immune response to sheep erythrocytes by phosphodiesterase-inhibiting dipyridamole derivatives.Journal of Immunopharmacology,6, 43–55.

    PubMed  Google Scholar 

  27. Lotan, R., andNicolson, G. L., 1988, Can anticancer therapy be improved by sequential use of cytotoxic and cytostatic (differentiating or immunomodulating) agents to suppress tumor cell phenotypic diversification.Biochemical Pharmacology,37, 149–154.

    PubMed  Google Scholar 

  28. Maniglia, C. A., Tudor, G., Gomez, J., andSartorelli, A., 1982, The effect of 2,6-bis(diethanolamin)-4-piperidinopyrimido 5,4-pyrimidine (RA 233) on growth, metastases, and lung colony formation of B16 melanoma.Cancer Letters,16, 253–260.

    PubMed  Google Scholar 

  29. Mareel, M. M., andDe Brabander, M., 1978, Effect of microtubule inhibitors on malignant invasionin vitro.Journal of the National Cancer Institute,41, 2349–2359.

    Google Scholar 

  30. Mareel, M. M., andDe Mets, M. J., 1984, Effect of microtubule inhibitors on invasion and on related activities of tumor cells.International Review of Cytology,90, 125–162.

    PubMed  Google Scholar 

  31. Neri, A., Welch, D., Kawaguchi, T., andNicolson, G. L., 1982, The development and biological properties of malignant cell sublines and clones of a spontaneously metastasizing rat mammary adenocarcinoma.Journal of the National Cancer Institute,68, 507–517.

    Google Scholar 

  32. Nicolson, G. L., 1982, Cancer metastasis: Organ colonization and the cell surface properties of malignant cells.Biochimica et Biophysica Acta,695, 113–176.

    PubMed  Google Scholar 

  33. Nicolson, G. L., andCustead, S. E., 1985, Effects of chemotherapeutic drugs on platelet and metastatic tumor cell-endothelial cell interactions as a model for assessing vascular endothelial integrity.Cancer Research,45, 331–336.

    PubMed  Google Scholar 

  34. Nicolson, G. L., Fidler, I. J., andPoste, G., 1986, Effects of tertiary amine local anesthetics on the blood-borne implantation and cell surface properties of metastatic mouse melanoma cells.Journal of the National Cancer Institute,76, 511–519.

    PubMed  Google Scholar 

  35. Nicolson, G. L., Irimura, T., Gonzalez, R., andRouslahti, E., 1981, The role of fibronectin in adhesion of metastatic melanoma cells to endothelial cells and their basal lamina.Experimental Cell Research,135, 464–465.

    Google Scholar 

  36. Nicolson, G. L., andLotan, R., 1986, Preventing diversification of malignant tumor cells during therapy.Clinical and Experimental Metastasis,4, 231–236.

    PubMed  Google Scholar 

  37. Ryd, W., andHagmar, B., 1984, The elimination of i.v. injected tumor cells. Studies with125IUDR labelled cells in four syngeneic murine tumor systems.Acta Pathologica et Microbiologica Scandinavica Sect. A,92, 23–30.

    Google Scholar 

  38. Schneider, B.,Geser, C., andFeuerer, W., 1987, Effect of anticoagulant treatment with RA 233 (Mopidamole) on survival in bronchial cancer.XI International Congress of Thrombosis and Haemostasis, Brussels, abstract, 1872.

  39. Segaloff, A., 1966, Hormones and breast cancer.Recent Progress in Hormone Research,22, 351–379.

    PubMed  Google Scholar 

  40. Stackpole, C. W., Fornabio, D. M., andAlterman, A. L., 1987, Failure of orally administered RA 233 to influence B16 melanoma growth or metastasis.Clinical and Experimental Metastasis,5, 165–180.

    PubMed  Google Scholar 

  41. Willmott, N., Malcolm, A., McLeod, T., Gracie, A., andCalman, K. C., 1983, Changes in anatomical distribution of tumor lesions induced by platelet-active drugs.Invasion and Metastasis,3, 32–51.

    Google Scholar 

  42. Zacharski, L. R., andMoritz, T. E., 1987, Effect of RA 233 (Mopidamole) on survival in carcinoma of the lung and colon. Final report of VA cooperative study #188.XI International Congress on Thrombosis and Haemostasis, Brussels, abstract, 1873.

  43. Zacharski, L. R., Moritz, T. E., Baczek, L. A., Rickles, F. R., Edwards, R. L., Forman, W. B., Forcier, R. J., Cornell, C. J., Haakenson, C. M., Ballard, H. S., Crum, E. D., Johnson, G. J., Levine, J., KiHong, W., O'Donnell, J. F., Schilsky, R. L., Ringenberg, Q. S., Robert, F., Spaulding, M. B., Tornyos, K., Williams, C., Zucker, S., Faulkner, C. S., II,Eaton, W. L., andHoppel, C. L., 1988, Effect of mopidamole on survival in carcinoma of the lung and colon: Final report of veterans administration cooperative study No. 188.Journal of the National Cancer Institute,80, 90–97.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lichtner, R.B., Erkell, L.J., Schirrmacher, V. et al. Effects of RA 233 treatment on the adhesive, invasive and metastatic properties of 13762NF rat mammary tumor cells. Clin Exp Metast 7, 175–186 (1989). https://doi.org/10.1007/BF01787022

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01787022

Keywords

Navigation