Thrombin Has a Bimodal Effect on Glioma Cell Growth

Overview

Journal Br J Cancer

Specialty Oncology

Date 1997 Jan 1

PMID 9413947

Citations 5

Authors

H Schafberg

G Nowak

R Kaufmann

Affiliations

Soon will be listed here.

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.

Citing Articles

A Novel Compound Targeting Protease Receptor 1 Activators for the Treatment of Glioblastoma.

Shavit-Stein E, Sheinberg E, Golderman V, Sharabi S, Wohl A, Gofrit S Front Neurol. 2019; 9:1087.

PMID: 30619047 PMC: 6304418. DOI: 10.3389/fneur.2018.01087.

The role of hormesis in the functional performance and protection of neural systems.

Calabrese E, Calabrese V, Giordano J Brain Circ. 2018; 3(1):1-13.

PMID: 30276298 PMC: 6126232. DOI: 10.4103/2394-8108.203257.

Thrombin Activity and Thrombin Receptor in Rat Glioblastoma Model: Possible Markers and Targets for Intervention?.

Itsekson-Hayosh Z, Shavit-Stein E, Last D, Goez D, Daniels D, Bushi D J Mol Neurosci. 2015; 56(3):644-51.

PMID: 25691153 DOI: 10.1007/s12031-015-0512-y.

Expression of proteinase-activated receptor 1-4 (PAR 1-4) in human cancer.

Elste A, Petersen I J Mol Histol. 2010; 41(2-3):89-99.

PMID: 20563836 DOI: 10.1007/s10735-010-9274-6.

Expression of functional protease-activated receptor 1 in human prostate cancer cell lines.

Liu J, Bastian M, Kohlschein P, Schuff-Werner P, Steiner M Urol Res. 2003; 31(3):163-8.

PMID: 12883880 DOI: 10.1007/s00240-003-0309-2.

References

Bar-Shavit R, Kahn A, Wilner G, Fenton 2nd J . Monocyte chemotaxis: stimulation by specific exosite region in thrombin. Science. 1983; 220(4598):728-31. DOI: 10.1126/science.6836310. View

Kaufmann R, Lindschau C, Hoer A, Henklein P, Adomeit A, Haller H . Signaling effects of alpha-thrombin and SFLLRN in rat glioma C6 cells. J Neurosci Res. 1996; 46(6):641-51. DOI: 10.1002/(SICI)1097-4547(19961215)46:6<641::AID-JNR1>3.0.CO;2-F. View

Zacharski L . Small cell carcinoma of the lung: interaction with the blood coagulation mechanism and treatment with anticoagulants. Onkologie. 1987; 10(4):264-70. DOI: 10.1159/000216419. View

Tas P, Koschel K . Thrombin reverts the beta-adrenergic agonist-induced morphological response in rat glioma C6 cells. Exp Cell Res. 1990; 189(1):22-7. DOI: 10.1016/0014-4827(90)90251-5. View

Rydel T, Ravichandran K, Tulinsky A, Bode W, Huber R, Roitsch C . The structure of a complex of recombinant hirudin and human alpha-thrombin. Science. 1990; 249(4966):277-80. DOI: 10.1126/science.2374926. View

Vu T, Hung D, Wheaton V, Coughlin S . Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991; 64(6):1057-68. DOI: 10.1016/0092-8674(91)90261-v. View

Nierodzik M, 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; 52(12):3267-72. View

Turner J, Redpath G, Humphries J, Gonias S, Vandenberg S . Plasmin modulates the thrombin-evoked calcium response in C6 glioma cells. Biochem J. 1994; 297 ( Pt 1):175-9. PMC: 1137807. DOI: 10.1042/bj2970175. View

Strawn L, Mann E, Elliger S, Chu L, Germain L, Niederfellner G . Inhibition of glioma cell growth by a truncated platelet-derived growth factor-beta receptor. J Biol Chem. 1994; 269(33):21215-22. View

10.

Barg J, Belcheva M, Zimlichman R, Levy R, Saya D, McHale R . Opioids inhibit endothelin-mediated DNA synthesis, phosphoinositide turnover, and Ca2+ mobilization in rat C6 glioma cells. J Neurosci. 1994; 14(10):5858-64. PMC: 2504522. View

11.

Herbert J, Dupuy E, Laplace M, Zini J, Bar Shavit R, Tobelem G . Thrombin induces endothelial cell growth via both a proteolytic and a non-proteolytic pathway. Biochem J. 1994; 303 ( Pt 1):227-31. PMC: 1137580. DOI: 10.1042/bj3030227. View

12.

Plantier J, Berthier R, Rival Y, Schweitzer A, Rabiet M . Evidence for a selective inhibitory effect of thrombin on megakaryocyte progenitor growth mediated by the thrombin receptor. Br J Haematol. 1994; 87(4):755-62. DOI: 10.1111/j.1365-2141.1994.tb06735.x. View

13.

Chen L, Buchanan J . Mitogenic activity of blood components. I. Thrombin and prothrombin. Proc Natl Acad Sci U S A. 1975; 72(1):131-5. PMC: 432255. DOI: 10.1073/pnas.72.1.131. View

14.

Glenn K, Carney D, Fenton 2nd J, Cunningham D . Thrombin active site regions required for fibroblast receptor binding and initiation of cell division. J Biol Chem. 1980; 255(14):6609-16. View

15.

Wojtukiewicz M, Tang D, Ben-Josef E, Renaud C, Walz D, Honn K . Solid tumor cells express functional "tethered ligand" thrombin receptor. Cancer Res. 1995; 55(3):698-704. View

16.

Takano S, Gately S, Engelhard H, Tsanaclis A, Brem S . Suramin inhibits glioma cell proliferation in vitro and in the brain. J Neurooncol. 1994; 21(3):189-201. DOI: 10.1007/BF01063768. View

17.

Nanevicz T, Ishii M, Wang L, Chen M, Chen J, Turck C . Mechanisms of thrombin receptor agonist specificity. Chimeric receptors and complementary mutations identify an agonist recognition site. J Biol Chem. 1995; 270(37):21619-25. DOI: 10.1074/jbc.270.37.21619. View

18.

Czubayko U, Reiser G . [Ca2+]i oscillations in single rat glioma cells induced by thrombin through activation of cell surface receptors. Neuroreport. 1995; 6(9):1249-52. DOI: 10.1097/00001756-199506090-00005. View

19.

Hollenberg M . Protease-mediated signalling: new paradigms for cell regulation and drug development. Trends Pharmacol Sci. 1996; 17(1):3-6. DOI: 10.1016/0165-6147(96)81562-8. View

20.

Carney D, Scott D, Gordon E, LaBelle E . Phosphoinositides in mitogenesis: neomycin inhibits thrombin-stimulated phosphoinositide turnover and initiation of cell proliferation. Cell. 1985; 42(2):479-88. DOI: 10.1016/0092-8674(85)90105-9. View