Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1978 Mar;37(3):424–433. doi: 10.1038/bjc.1978.63

Fibrinolytic Activity of Cultured Cells Derived During Ethylnitrosourea-induced Carcinogenesis of Rat Brain

T A Hince, J P Roscoe
PMCID: PMC2009526  PMID: 638021

Abstract

Using a fibrin-agarose-overlay technique, high levels of plasminogen-dependent fibrinolytic activity have been demonstrated in cell lines derived from an ethylnitrosourea-induced glioma of the rat brain. Cell lines derived from normal adult rat brain showed only low levels of activity. The degree of lysis produced by a cell line was dependent on the average number of cells per colony, and a different pattern of response was observed for tumour and normal cell lines. A good positive correlation existed between the level of fibrinolytic activity, growth in agar and tumourigenicity of a cell line. Fibrinolytic activity was associated with cell lines derived at various times in the latent period, before the appearance of a visible tumour. Many cell lines derived from rat brains at 57-60 (E7), 90-91 (E8) and 111-112 (E6) days after transplacental exposure to ethylnitrosourea showed fibrinolytic activity, and in the latter group the close association with growth in agar and tumourigenicity was also demonstrated. Results from cell lines derived in the E7 and E8 experiments indicated that the possession of fibrinolytic activity preceded the ability of cells to form colonies in agar.

Full text

PDF
424

Images in this article

426Fig. 1
on p.426
427Fig. 2
on p.427

Selected References

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

  1. ALKJAERSIG N., FLETCHER A. P., SHERRY S. xi-Aminocaproic acid: an inhibitor of plasminogen activation. J Biol Chem. 1959 Apr;234(4):832–837. [PubMed] [Google Scholar]
  2. Astedt B., Holmberg L. Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture. Nature. 1976 Jun 17;261(5561):595–597. doi: 10.1038/261595a0. [DOI] [PubMed] [Google Scholar]
  3. Bernik M. B., Kwaan H. C. Plasminogen activator activity in cultures from human tissues. An immunological and histochemical study. J Clin Invest. 1969 Sep;48(9):1740–1753. doi: 10.1172/JCI106140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Christman J. K., Acs G. Purification and characterization of a cellular fibrinolytic factor associated with oncogenic transformation: the plasminogen activator from SV-40-transformed hamster cells. Biochim Biophys Acta. 1974 Mar 27;340(3):339–347. doi: 10.1016/0005-2787(74)90279-2. [DOI] [PubMed] [Google Scholar]
  5. Claisse P. J., Roscoe J. P. The inducibility of glycerol phosphate dehydrogenase in two rat glial clones. Brain Res. 1976 Jun 11;109(2):423–425. doi: 10.1016/0006-8993(76)90547-3. [DOI] [PubMed] [Google Scholar]
  6. Druckrey H., Ivanković S., Preussmann R. Teratogenic and carcinogenic effects in the offspring after single injection of ethylnitrosourea to pregnant rats. Nature. 1966 Jun 25;210(5043):1378–1379. doi: 10.1038/2101378a0. [DOI] [PubMed] [Google Scholar]
  7. Jones P. A., Laug W. E., Gardner A., Nye C. A., Fink L. M., Benedict W. F. In vitro correlates of transformation in C3H/10T1/2 clone 8 mouse cells. Cancer Res. 1976 Aug;36(8):2863–2867. [PubMed] [Google Scholar]
  8. Jones P., Benedict W., Strickland S., Reich E. Fibrin overlay methods for the detection of single transformed cells and colonies of transformed cells. Cell. 1975 Jul;5(3):323–329. doi: 10.1016/0092-8674(75)90108-7. [DOI] [PubMed] [Google Scholar]
  9. Lantos P. L., Roscoe J. P., Skidmore C. J. Studies of the morphology and tumorigenicity of experimental brain tumours in tissue culture. Br J Exp Pathol. 1976 Feb;57(1):95–104. [PMC free article] [PubMed] [Google Scholar]
  10. Lantos P. L. The fine structure of periventricular pleomorphic gliomas induced transplacentally by N-ethyl-N-nitrosourea in BD-IX rats. With a note on their origin. J Neurol Sci. 1972 Dec;17(4):443–460. doi: 10.1016/0022-510x(72)90156-6. [DOI] [PubMed] [Google Scholar]
  11. Laug W. E., Jones P. A., Benedict W. F. Relationship between fibrinolysis of cultured cells and malignancy. J Natl Cancer Inst. 1975 Jan;54(1):173–179. doi: 10.1093/jnci/54.1.173. [DOI] [PubMed] [Google Scholar]
  12. Nagy B., Ban J., Brdar B. Fibrinolysis associated with human neoplasia: production of plasminogen activator by human tumours. Int J Cancer. 1977 May 15;19(5):614–620. doi: 10.1002/ijc.2910190504. [DOI] [PubMed] [Google Scholar]
  13. Ossowski L., Unkeless J. C., Tobia A., Quigley J. P., Rifkin D. B., Reich E. An enzymatic function associated with transformation of fibroblasts by oncogenic viruses. II. Mammalian fibroblast cultures transformed by DNA and RNA tumor viruses. J Exp Med. 1973 Jan 1;137(1):112–126. doi: 10.1084/jem.137.1.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pearlstein E., Hynes R. O., Franks L. M., Hemmings V. J. Surface proteins and fibrinolytic activity of cultured mammalian cells. Cancer Res. 1976 Apr;36(4):1475–1480. [PubMed] [Google Scholar]
  15. Pollack R., Risser R., Conlon S., Rifkin D. Plasminogen activator production accompanies loss of anchorage regulation in transformation of primary rat embryo cells by simian virus 40. Proc Natl Acad Sci U S A. 1974 Dec;71(12):4792–4796. doi: 10.1073/pnas.71.12.4792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Quigley J. P., Ossowski L., Reich E. Plasminogen, the serum proenzyme activated by factors from cells transformed by oncogenic viruses. J Biol Chem. 1974 Jul 10;249(13):4306–4311. [PubMed] [Google Scholar]
  17. Rifkin D. B., Pollack R. Production of plasminogen activator by established cell lines of mouse origin. J Cell Biol. 1977 Apr;73(1):47–55. doi: 10.1083/jcb.73.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Roscoe J. P., Claisse P. J. A sequential in vivo-in vitro study of carcinogenesis induced in the rat brain by ethylnitrosourea. Nature. 1976 Jul 22;262(5566):314–316. doi: 10.1038/262314a0. [DOI] [PubMed] [Google Scholar]
  19. Schultz D. R., Wu M. C., Yunis A. A. Immunologic relationship among fibrinolysins secreted by cultured mammalian tumor cells. Exp Cell Res. 1975 Nov;96(1):47–57. doi: 10.1016/s0014-4827(75)80035-8. [DOI] [PubMed] [Google Scholar]
  20. Strickland S., Reich E., Sherman M. I. Plasminogen activator in early embryogenesis: enzyme production by trophoblast and parietal endoderm. Cell. 1976 Oct;9(2):231–240. doi: 10.1016/0092-8674(76)90114-8. [DOI] [PubMed] [Google Scholar]
  21. Unkeless J., Dano K., Kellerman G. M., Reich E. Fibrinolysis associated with oncogenic transformation. Partial purification and characterization of the cell factor, a plasminogen activator. J Biol Chem. 1974 Jul 10;249(13):4295–4305. [PubMed] [Google Scholar]
  22. Wu M., Arimura G. K., Yunis A. A. Purification and characterization of a plasminogen activator secreted by cultured human pancreatic carcinoma cells. Biochemistry. 1977 May 3;16(9):1908–1913. doi: 10.1021/bi00628a023. [DOI] [PubMed] [Google Scholar]

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

RESOURCES