Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1991 Sep;64(3):513–517. doi: 10.1038/bjc.1991.340

Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved.

A D Purushotham 1, P McCulloch 1, W D George 1
PMCID: PMC1977674  PMID: 1911192

Abstract

Warfarin inhibits metastasis in the animal model and injection of the Warfarin-dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacrifice at various intervals, measured lung radioactivity was significantly higher (20%) in animals administered cells with the factor complex than in the other two groups (P less than 0.001, ANOVA and Student's t-test). These results indicate increased entrapment of tumour cells in the pulmonary microcirculation. In a second experiment, rat factor complex II, IX, X was prepared, and Mtln3 cells were then injected in female Fisher 344 rats alone or in combination with either human factor complex or rat factor complex. Following sacrifice, the number of pulmonary nodules in animals receiving cells with rat factor complex was similar to that in animals receiving human factor complex, and significantly higher than that in the control (P less than 0.001, ANOVA and Mann-Whitney), indicating that the observed enhancement of pulmonary seeding is unrelated to the xenogeneic properties of the human factor complex.

Full text

PDF
513

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahmad S. S., Rawala-Sheikh R., Thompson A. R., Walsh P. N. Rapid purification of factor IX, factor X and prothrombin by immunoaffinity and ion exchange chromatography. Thromb Res. 1989 Jul 1;55(1):121–133. doi: 10.1016/0049-3848(89)90462-3. [DOI] [PubMed] [Google Scholar]
  2. Brown J. M. A study of the mechanism by which anticoagulation with warfarin inhibits blood-borne metastases. Cancer Res. 1973 Jun;33(6):1217–1224. [PubMed] [Google Scholar]
  3. Coppen A., Ghose K., Montgomery S., Rama Rao V. A., Bailey J., Christiansen J., Mikkleson P. L., van Praag H. M., van de Poel F., Minsker E. J. Amitriptyline plasma-concentration and clinical effect. A World Health Organisation Collaborative Study. Lancet. 1978 Jan 14;1(8055):63–66. doi: 10.1016/s0140-6736(78)90003-x. [DOI] [PubMed] [Google Scholar]
  4. Crissman J. D., Hatfield J., Schaldenbrand M., Sloane B. F., Honn K. V. Arrest and extravasation of B16 amelanotic melanoma in murine lungs. A light and electron microscopic study. Lab Invest. 1985 Oct;53(4):470–478. [PubMed] [Google Scholar]
  5. Fidler I. J. Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125 I-5-iodo-2'-deoxyuridine. J Natl Cancer Inst. 1970 Oct;45(4):773–782. [PubMed] [Google Scholar]
  6. Hilgard P., Schulte H., Wetzig G., Schmitt G., Schmidt C. G. Oral anticoagulation in the treatment of a spontaneously metastasising murine tumour (3LL). Br J Cancer. 1977 Jan;35(1):78–86. doi: 10.1038/bjc.1977.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. McCulloch P., George W. D. Promotion of metastasis by a specific complex of coagulation factors may be independent of fibrin formation. Br J Cancer. 1988 Aug;58(2):158–162. doi: 10.1038/bjc.1988.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McCulloch P., George W. D. Warfarin inhibition of metastasis: the role of anticoagulation. Br J Surg. 1987 Oct;74(10):879–883. doi: 10.1002/bjs.1800741005. [DOI] [PubMed] [Google Scholar]
  9. Neri A., Nicolson G. L. Phenotypic drift of metastatic and cell-surface properties of mammary adenocarcinoma cell clones during growth in vitro. Int J Cancer. 1981 Dec;28(6):731–738. doi: 10.1002/ijc.2910280612. [DOI] [PubMed] [Google Scholar]
  10. Neri A., Welch D., Kawaguchi T., Nicolson G. L. Development and biologic properties of malignant cell sublines and clones of a spontaneously metastasizing rat mammary adenocarcinoma. J Natl Cancer Inst. 1982 Mar;68(3):507–517. [PubMed] [Google Scholar]
  11. O'Meara R. A. Fibrin formation and tumour growth. Thromb Diath Haemorrh Suppl. 1968;28:137–168. [PubMed] [Google Scholar]
  12. Plumb J. A., Milroy R., Kaye S. B. Effects of the pH dependence of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan absorption on chemosensitivity determined by a novel tetrazolium-based assay. Cancer Res. 1989 Aug 15;49(16):4435–4440. [PubMed] [Google Scholar]
  13. Rickles F. R., Edwards R. L. Activation of blood coagulation in cancer: Trousseau's syndrome revisited. Blood. 1983 Jul;62(1):14–31. [PubMed] [Google Scholar]
  14. Ryan J. J., Ketcham A. S., Wexler H. Reduced incidence of spontaneous metastases with long-term Coumadin therapy. Ann Surg. 1968 Jul;168(1):163–168. doi: 10.1097/00000658-196807000-00021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ryan J. J., Ketcham A. S., Wexler H. Warfarin therapy as an adjunct to the surgical treatment of malignant tumors in mice. Cancer Res. 1969 Dec;29(12):2191–2194. [PubMed] [Google Scholar]
  16. Segaloff A. Hormones and breast cancer. Recent Prog Horm Res. 1966;22:351–379. doi: 10.1016/b978-1-4831-9825-5.50012-9. [DOI] [PubMed] [Google Scholar]
  17. Sindelar W. F., Tralka T. S., Ketcham A. S. Electron microscopic observations on formation of pulmonary metastases. J Surg Res. 1975 Feb;18(2):137–161. doi: 10.1016/0022-4804(75)90010-4. [DOI] [PubMed] [Google Scholar]
  18. Sun N. C., McAfee W. M., Hum G. J., Weiner J. M. Hemostatic abnormalities in malignancy, a prospective study of one hundred eight patients. Part I. Coagulation studies. Am J Clin Pathol. 1979 Jan;71(1):10–16. doi: 10.1093/ajcp/71.1.10. [DOI] [PubMed] [Google Scholar]
  19. WOOD S., Jr Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. AMA Arch Pathol. 1958 Oct;66(4):550–568. [PubMed] [Google Scholar]
  20. Wexler H. Accurate identification of experimental pulmonary metastases. J Natl Cancer Inst. 1966 Apr;36(4):641–645. doi: 10.1093/jnci/36.4.641. [DOI] [PubMed] [Google Scholar]
  21. Williamson R. C., Lyndon P. J., Tudway A. J. Effects of anticoagulation and ileal resection on the development and spread of experimental intestinal carcinomas. Br J Cancer. 1980 Jul;42(1):85–94. doi: 10.1038/bjc.1980.206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wood S., Jr Experimental studies on the spread of cancer, with special reference to fibrinolytic agents and anticoagulants. J Med. 1974;5(1):7–22. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES