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British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(12):1592–1595. doi: 10.1038/bjc.1997.602

Thrombin has a bimodal effect on glioma cell growth.

H Schafberg 1, G Nowak 1, R Kaufmann 1
PMCID: PMC2228214  PMID: 9413947

Abstract

Using rat glioma C6 cells as a model, we have found a bimodal effect of alpha-thrombin on cell growth. In C6 cells treated with alpha-thrombin at concentrations from 0.02 nM to 1.0 nM, inhibition of cell proliferation was noted. Because the thrombin receptor agonist peptide TRAP-6 also induced inhibition of cell proliferation and the thrombin receptor antagonist peptide T1 prevented the inhibitory effect of alpha-thrombin on C6 glioma cell growth, thrombin receptor involvement in antiproliferative action of alpha-thrombin in C6 glioma cells is highly likely. However, stimulation of cell proliferation observed when C6 cells were treated with alpha-thrombin at higher doses (> 1.0 nM) seems to be mediated by as yet undefined thrombin receptor-independent biochemical mechanisms.

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Selected References

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  1. Bar-Shavit R., Kahn A., Wilner G. D., Fenton J. W., 2nd Monocyte chemotaxis: stimulation by specific exosite region in thrombin. Science. 1983 May 13;220(4598):728–731. doi: 10.1126/science.6836310. [DOI] [PubMed] [Google Scholar]
  2. Barg J., Belcheva M. M., Zimlichman R., Levy R., Saya D., McHale R. J., Johnson F. E., Coscia C. J., Vogel Z. Opioids inhibit endothelin-mediated DNA synthesis, phosphoinositide turnover, and Ca2+ mobilization in rat C6 glioma cells. J Neurosci. 1994 Oct;14(10):5858–5864. doi: 10.1523/JNEUROSCI.14-10-05858.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carney D. H., Scott D. L., Gordon E. A., LaBelle E. F. Phosphoinositides in mitogenesis: neomycin inhibits thrombin-stimulated phosphoinositide turnover and initiation of cell proliferation. Cell. 1985 Sep;42(2):479–488. doi: 10.1016/0092-8674(85)90105-9. [DOI] [PubMed] [Google Scholar]
  4. Chen L. B., Buchanan J. M. Mitogenic activity of blood components. I. Thrombin and prothrombin. Proc Natl Acad Sci U S A. 1975 Jan;72(1):131–135. doi: 10.1073/pnas.72.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Czubayko U., Reiser G. [Ca2+]i oscillations in single rat glioma cells induced by thrombin through activation of cell surface receptors. Neuroreport. 1995 Jun 19;6(9):1249–1252. doi: 10.1097/00001756-199506090-00005. [DOI] [PubMed] [Google Scholar]
  6. Glenn K. C., Carney D. H., Fenton J. W., 2nd, Cunningham D. D. Thrombin active site regions required for fibroblast receptor binding and initiation of cell division. J Biol Chem. 1980 Jul 25;255(14):6609–6616. [PubMed] [Google Scholar]
  7. Herbert J. M., Dupuy E., Laplace M. C., Zini J. M., Bar Shavit R., Tobelem G. Thrombin induces endothelial cell growth via both a proteolytic and a non-proteolytic pathway. Biochem J. 1994 Oct 1;303(Pt 1):227–231. doi: 10.1042/bj3030227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hollenberg M. D. Protease-mediated signalling: new paradigms for cell regulation and drug development. Trends Pharmacol Sci. 1996 Jan;17(1):3–6. doi: 10.1016/0165-6147(96)81562-8. [DOI] [PubMed] [Google Scholar]
  9. Kaufmann R., Lindschau C., Höer A., Henklein P., Adomeit A., Haller H., Liebmann C., Oberdisse E., Nowak G. Signaling effects of alpha-thrombin and SFLLRN in rat glioma C6 cells. J Neurosci Res. 1996 Dec 15;46(6):641–651. doi: 10.1002/(SICI)1097-4547(19961215)46:6<641::AID-JNR1>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  10. Nanevicz T., Ishii M., Wang L., Chen M., Chen J., Turck C. W., Cohen F. E., Coughlin S. R. Mechanisms of thrombin receptor agonist specificity. Chimeric receptors and complementary mutations identify an agonist recognition site. J Biol Chem. 1995 Sep 15;270(37):21619–21625. doi: 10.1074/jbc.270.37.21619. [DOI] [PubMed] [Google Scholar]
  11. Nierodzik M. L., Kajumo F., Karpatkin S. Effect of thrombin treatment of tumor cells on adhesion of tumor cells to platelets in vitro and tumor metastasis in vivo. Cancer Res. 1992 Jun 15;52(12):3267–3272. [PubMed] [Google Scholar]
  12. Plantier J. L., Berthier R., Rival Y., Schweitzer A., Rabiet M. J. Evidence for a selective inhibitory effect of thrombin on megakaryocyte progenitor growth mediated by the thrombin receptor. Br J Haematol. 1994 Aug;87(4):755–762. doi: 10.1111/j.1365-2141.1994.tb06735.x. [DOI] [PubMed] [Google Scholar]
  13. Rydel T. J., Ravichandran K. G., Tulinsky A., Bode W., Huber R., Roitsch C., Fenton J. W., 2nd The structure of a complex of recombinant hirudin and human alpha-thrombin. Science. 1990 Jul 20;249(4966):277–280. doi: 10.1126/science.2374926. [DOI] [PubMed] [Google Scholar]
  14. Strawn L. M., Mann E., Elliger S. S., Chu L. M., Germain L. L., Niederfellner G., Ullrich A., Shawver L. K. Inhibition of glioma cell growth by a truncated platelet-derived growth factor-beta receptor. J Biol Chem. 1994 Aug 19;269(33):21215–21222. [PubMed] [Google Scholar]
  15. Takano S., Gately S., Engelhard H., Tsanaclis A. M., Brem S. Suramin inhibits glioma cell proliferation in vitro and in the brain. J Neurooncol. 1994;21(3):189–201. doi: 10.1007/BF01063768. [DOI] [PubMed] [Google Scholar]
  16. Tas P. W., Koschel K. Thrombin reverts the beta-adrenergic agonist-induced morphological response in rat glioma C6 cells. Exp Cell Res. 1990 Jul;189(1):22–27. doi: 10.1016/0014-4827(90)90251-5. [DOI] [PubMed] [Google Scholar]
  17. Turner J. S., Redpath G. T., Humphries J. E., Gonias S. L., Vandenberg S. R. Plasmin modulates the thrombin-evoked calcium response in C6 glioma cells. Biochem J. 1994 Jan 1;297(Pt 1):175–179. doi: 10.1042/bj2970175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Vu T. K., Hung D. T., Wheaton V. I., Coughlin S. R. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991 Mar 22;64(6):1057–1068. doi: 10.1016/0092-8674(91)90261-v. [DOI] [PubMed] [Google Scholar]
  19. Wojtukiewicz M. Z., Tang D. G., Ben-Josef E., Renaud C., Walz D. A., Honn K. V. Solid tumor cells express functional "tethered ligand" thrombin receptor. Cancer Res. 1995 Feb 1;55(3):698–704. [PubMed] [Google Scholar]
  20. Zacharski L. R. Small cell carcinoma of the lung: interaction with the blood coagulation mechanism and treatment with anticoagulants. Onkologie. 1987 Aug;10(4):264–270. doi: 10.1159/000216419. [DOI] [PubMed] [Google Scholar]

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