|
|
|
|
|
|
||
|
|
||||
|
|
||||
|
||||
Tumor Biology |
Departments of Neurosurgery [A.G., E.L.K., S.Z., J.D., M.W.] and Neuropathology [C.H.], University Hospital Eppendorf, 20246 Hamburg, Germany; Neuro-Oncology Laboratory [M.E.B.], Barrow Neurological Institute, Phoenix, AZ 85013-4496
2 Address correspondence and reprint requests to Alf Giese, MD, Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, 20246 Hamburg, Germany.
Abstract
The capacity of glial tumor cells to migrate and diffusely infiltrate normal brain compromises surgical eradication of the disease. Identification of genes associated with invasion may offer novel strategies for anti-invasive therapies. The gene for TXsyn, an enzyme of the arachidonic acid pathway, has been identified by differential mRNA display as being overexpressed in a glioma cell line selected for migration. In this study TXsyn mRNA expression was found in a large panel of glioma cell lines but not in a strain of human astrocytes. Immunohistochemistry demonstrated TXsyn in the parenchyma of glial tumors and in reactive astrocytes, whereas it could not be detected in quiescent astrocytes and oligodendroglia of normal brain. Glioma cell lines showed a wide range of thromboxane B2 formation, the relative expression of which correlated with migration rates of these cells. Migration was effectively blocked by specific inhibitors of TXsyn, such as furegrelate and dazmegrel. Other TXsyn inhibitors and cyclooxygenase inhibitors were less effective. Treatment with specific inhibitors also resulted in a decrease of intercellular adhesion in glioma cells. These data indicate that TXsyn plays a crucial role in the signal transduction of migration in glial tumors and may offer a novel strategy for anti-invasive therapies.
References
Aas, A.T., Tonnessen, T.I., Brun, A., and Salford, L.G. (1995) Growth inhibition of rat glioma cells in vitro and in vivo by aspirin. J. Neurooncol. 24,171 -180.[CrossRef][Medline]
Amberger, V.R., Paganetti, P.A., Seulberger, H., Eldering, J.A.,
and Schwab, M.E. (1994) Characterization of a membrane-bound
metalloendoprotease of rat C6 glioblastoma cells. Cancer
Res. 54,4017
-4025.
Asch, A.S., Leung, L.L., Shapiro, J.R., and Nachmann, R.L
(1986) Human brain glia cells synthesize thrombospondin.
Proc. Natl. Acad. Sci. U. S. A.
83,2904
-2908.
Auch-Schwelk, W., Katusic, Z.S., and Vanhoutte, P.M.
(1990) Thromboxane A2 receptor antagonists inhibit
endothelium-dependent contractions. Hypertension
15,699
-703.
Berens, M.E., Rief, M.D., Loo, M.A., and Giese, A. (1994) The role of extracellular matrix in human astrocytoma migration and proliferation studied in a microliter scale assay. Clin. Exp. Metastasis 12,405 -415.[CrossRef][ISI][Medline]
Bernstein, J.J., Laws, E.R., Jr., Levine, K.V., Wood, L.R., Tadvalkar, G., and Goldberg, W.J. (1991) C6 glioma-astrocytoma cell and fetal astrocyte migration into artificial basement membrane: A permissive substrate for neural tumors but not fetal astrocytes. Neurosurgery 28,652 -658.[CrossRef][ISI][Medline]
Brass, L.F., Manning, D.R., Cichowski, K., and Abrams, C.S. (1997) Signaling through G proteins in platelets: To the integrins and beyond. Thromb. Haemost. 78,581 -589.[ISI][Medline]
Breder, C.D., Smith, W.L., Raz, A., Masferrer, J., Seibert, K., Needleman, P., and Saper, C.B. (1992) Distribution and characterization of cyclooxygenase immunoreactivity in the ovine brain. J. Comp. Neurol. 322,409 -438.[CrossRef][ISI][Medline]
Bryant, J. (1994) Correlation between metastatic patterns in renal cell carcinoma and tissue distribution of thromboxane synthase. Acta. Oncol. 33,708 -709.[ISI][Medline]
Castelli, M.G., Chiabrando, C., Fanelli, R., Martelli, L., Butti,
G., Gaetani, P., and Paoletti, P. (1989) Prostaglandin and
thromboxane synthesis by human intracranial tumors. Cancer
Res. 49,1505
-1508.
Conde, B., Tejedor, M., Sinues, E., and Alcala, A. (1991) Modulation of cell growth and differentiation induced by prostaglandin D2 in the glioma cell line C6. Anticancer Res. 11,289 -295.[ISI][Medline]
Gaetani, P., Butti, G., Chiabrando, C., Danova, M., Castelli, M.G., Riccardi, A., Assietti, R., and Paoletti, P. (1991) A study on the biological behavior of human brain tumors. Part I. Arachidonic acid metabolism and DNA content. J. Neurooncol. 10,233 -240.[Medline]
Gati, I., Bergstrom, M., Westerberg, G., Csoka, K., Muhr, C., and Carlsson, J. (1990) Effects of prostaglandin and leukotriene inhibitors on the growth of human glioma spheroids. Eur. J. Cancer 26,802 -807.
Giese, A., and Westphal, M. (1996) Glioma invasion in the central nervous system. Neurosurgery 39,235 -252.[CrossRef][ISI][Medline]
Giese, A., Rief, M.D., Loo, M.A., and Berens, M.E.
(1994) Determinants of human astrocytoma migration.
Cancer Res. 54,3897
-3904.
Giese, A., Loo, M.A., Rief, M.D., Tran, N., and Berens, M.E. (1995) Substrates for astrocytoma invasion. Neurosurgery 37,294 -302.[ISI][Medline]
Giese, A., Kluwe, L., Laube, B., Meissner, H., Berens, M.E., and Westphal, M. (1996a) Migration of human glioma cells on myelin. Neurosurgery 38,755 -764.[CrossRef][ISI][Medline]
Giese, A., Loo, M.A., Tran, N., Haskett, D., Coons, S.W., and Berens, M.E. (1996b) Dichotomy of astrocytoma migration and proliferation. Int. J. Cancer 67,275 -282.[CrossRef][ISI][Medline]
Giese, A., Loo, M.A., Norman, S.A., Treasurywala, S., and Berens, M.E. (1996c) Contrasting migratory response of astrocytoma cells to tenascin mediated by different integrins. J. Cell Sci. 109,2161 -2168.[Abstract]
Giese, A., Laube, B., Zapf, S., and Westphal, M. (1998) Glioma cell adhesion and migration on human brain sections. Anticancer Res. 18,2435 -2447.[ISI][Medline]
Gorman, R.R. (1983) Biology and biochemistry of thromboxane synthetase inhibitors. Adv. Prostaglandin Thromboxane Leukot. Res. 11,235 -240.[ISI][Medline]
Gresele, P., Deckmyn, H., Nenci, G.G., and Vermylen, J. (1991) Thromboxane synthase inhibitors, thromboxane receptor antagonists and dual blockers in thrombotic disorders. Trenda Pharmacol. Sci. 12,158 -163.
Hayaishi, O. (1991) Molecular mechanisms of sleep-wake regulation: Roles of prostaglandins D2 and E2. FASEB J. 5,2575 -2581.[Abstract]
Hertting, G., and Seregi, A. (1989) Formation and function of eicosanoids in the central nervous system. Ann. N. Y. Acad. Sci. 559,84 -99.[ISI][Medline]
Huang, M.M., Lipfert, L., Cunningham, M., Brugge, J.S., Ginsberg,
M.H., and Shattil, S.J. (1993) Adhesive ligand binding to
integrin aIIbb3 stimulates tyrosine phosphorylation of novel protein
substrates before phosphorylation of pp125FAK. J. Cell
Biol. 122,473
-483.
Inagaki, N., and Wada, H. (1994) Histamine and prostanoid receptors on glial cells. Glia 11,102 -109.[CrossRef][ISI][Medline]
Kitanaka, J., Hashimoto, H., Gotoh, M., Kondo, K., Sakata, K., Hirasawa, Y., Sawada, M., Suzumura, A., Marunouchi, T., Matsuda, T., and Baba, A. (1996) Expression pattern of messenger RNAs for prostanoid receptors in glial cell cultures. Brain Res. 707,282 -287.[CrossRef][ISI][Medline]
Kornberg, L.J., Earp, H.S., Turner, C.E., Prockop, C., and Juliano,
R.L. (1991) Signal transduction by integrins: Increased protein
tyrosine phosphorylation caused by clustering of b1 integrins.
Proc. Natl. Acad. Sci. U. S. A.
88,8392
-8396.
Kramer, R., McDonald, K.A., Crowley, E., Ramos, D., and Damsky,
C.H. (1989) Integrin related complex mediate the adhesion of
melanoma cells to basement membrane. Cancer Res.
49,393
-402.
Luna, E.J., and Hitt, A.L. (1992)
Cytoskeleton-membrane interactions. Science
258,955
-964.
McDonough, W., Tran, N., Giese, A., Norman, S.A., and Berens, M.E. (1998) Altered gene expression in human astrocytoma cells selected for migration. I. Thromboxane synthase. J. Neuropathol. Exp. Neurol. 55,449 -455.
Mohrland, J.S., Vander Lugt, J.T., Gorman, R.R., and Lakings, D.B. (1989) Thromboxane synthase activity and platelet function after furegrelate administration in man. J. Clin. Pharmacol. 29, 53-58.[Abstract]
Moncada, S., and Vane, J.R. (1979) Arachidonic acid metabolites and the interaction between platelets and blood-vessel walls. N. Engl. J. Med. 300,1142 -1147.[ISI][Medline]
Nanji, A.A. (1993) Thromboxane synthase and organ
preference for metastases. N. Engl. J. Med.
329, 138-139.
(Letter)
Negishi, M., Sugimoto, Y., and Ichikawa, A. (1995) Molecular mechanisms of diverse actions of prostanoid receptors. Biochem. Biophys. Acta. 1259,109 -119.[Medline]
Nüsing, R., and Ullrich, V. (1990) Immunoquantitation of thromboxane synthase in human tissues. Eicosanoids 3,175 -180.[ISI][Medline]
Nüsing, R., Wernet, M.P., and Ullrich, V. (1990)
Production and characterization of polyclonal and monoclonal antibodies
against human thromboxane synthase. Blood
76, 80-85.
Pasquier, B., Pasquier, D., N`Golet, A., Panh, M.H., and Couderc, P. (1980) Extraneural metastases of astrocytomas and glioblastomas: Clinicopathological study of two cases and review of literature. Cancer 45,112 -125.[CrossRef][ISI][Medline]
Paulus, W., and Tonn, J.C. (1994) Basement membrane invasion of glioma cells mediated by integrin receptors. J. Neurosurg. 80,515 -519.[ISI][Medline]
Paulus, W., Baur, I., Schuppan, D., and Roggendorf, W. (1993) Characterization of integrin receptors in normal and neoplastic human brain. Am. J. Pathol. 143,154 -163.[Abstract]
Paulus, W., Baur, I., Beutler, A.S., and Reeves, S.A. (1996) Diffuse brain invasion of glioma cells requires b1 integrins. Lab. Invest. 75,819 -826.[ISI][Medline]
Schrör, K. (1995) Antiplatelet drugs. A comparative review. Drugs 50, 7-28.[ISI][Medline]
Schwartz, J.C., Arrang, J.M., Garbarg, M., Pollard, H., and Ruat,
M. (1991) Histaminergic transmission in the mammalian brain.
Physiol. Rev. 71,1
-51.
Shattil, S.J., Haimovich, B., Cunningham, M., Lipfert, L., Parsons,
J.T., Ginsberg, M.H., and Brugge, J.S. (1994) Tyrosine
phosphorylation of pp125 FAK in platelets requires coordinated signaling
through integrin and agonist receptors. J. Biol. Chem.
269,14738
-14745.
Vermylen, J., and Deckmyn, H. (1992) Thromboxane synthase inhibitors and receptor antagonists. Cardiovasc. Drugs Ther. 6,29 -33.[ISI][Medline]
Westphal, M., Neuss, M., and Herrmann, H.D. (1986) Prostaglandins: Antiproliferative effect of PGD 2 on cultured human glioma cells. Acta. Neurochir. 83, 56-61.
Wolfe, L.S. (1982) Eicosanoids: Prostaglandins, thromboxanes, leukotrienes, and other derivatives of carbon-20 unsaturated fatty acids. J. Neurochem. 38, 1-14.[CrossRef][ISI][Medline]
Wynalda, M.A., Liggett, W.F., and Fitzpatrick, F.A. (1983) Sodium 5-(39-pyridinylmethyl) benzofuran-2-carboxylate (U-63557A), a new, selective thromboxane synthase inhibitor: Intravenous and oral pharmacokinetics in dogs and correlation with ex situ thromboxane B2 production. Prostaglandins 26,311 -324.[CrossRef][ISI][Medline]
This article has been cited by other articles:
|
|
 |
|
  D. Nie, Y. Guo, D. Yang, Y. Tang, Y. Chen, M.-T. Wang, A. Zacharek, Y. Qiao, M. Che, and K. V. Honn Thromboxane A2 Receptors in Prostate Carcinoma: Expression and Its Role in Regulating Cell Motility via Small GTPase Rho Cancer Res., January 1, 2008; 68(1): 115 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Brockmann, A. Giese, K. Mueller, F. j. Kaba, F. Lohr, C. Weiss, S. Gottschalk, I. Nolte, J. Leppert, J. Tuettenberg, et al. Preoperative thrombocytosis predicts poor survival in patients with glioblastoma Neuro-oncol, July 1, 2007; 9(3): 335 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Giese, R. Bjerkvig, M.E. Berens, and M. Westphal Cost of Migration: Invasion of Malignant Gliomas and Implications for Treatment J. Clin. Oncol., April 15, 2003; 21(8): 1624 - 1636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Fenton, M. S. Wolff, M. W. Orth, and N. G. Hord Membrane-type matrix metalloproteinases mediate curcumin-induced cell migration in non-tumorigenic colon epithelial cells differing in Apc genotype Carcinogenesis, June 1, 2002; 23(6): 1065 - 1070. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
