Abstract
Objective: Our previous studies showed that thrombin contributes to brain edema in gliomas. The present study investigated the role of a thrombin receptor, protease activated receptor-1 (PAR-1), in edema formation in glioma models.
Methods: These experiments were performed in Fischer 344 rats, PAR-1 knockout mice, and wild-type C57BL/6 mice controls. F98 glioma cells were infused into the right caudate. Animals were euthanized and the brains were used for measurements of brain edema and PAR-1 expression.
Results: In rats, implantation of glioma cells resulted in significant brain edema in the ipsilateral hemisphere (82.6 ± ;1.4 vs. 78.1 ± 0.9 % in the contralateral hemisphere, p < 0.01). By Western blot analysis and RT-PCR, we found that both protein and mRNA levels of PAR-1 were upregulated in the glioma (p < 0.01). In mice, implantation of glioma cells also caused brain edema in the ipsilateral hemisphere (p < 0.05). Glioma-induced brain edema was less in PAR-1 knockout mice (day 12: 79.4 ;± 1.3 vs. 81.5 ± 1.1 % in the wild-type mice, p < ;0.05).
Conclusion: PAR-1 plays a role in glioma-induced brain edema. Clarification of the role of PAR-1 in edema formation should help to develop new therapeutic strategies for gliomas.
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References
Chang EF, Meeker M, Holland MC (2006) Acute traumatic intraparenchymal hemorrhage: risk factors for progression in the early post-injury period. Neurosurgery 58:647–656; discussion 647–656
Chinni C, de Niese MR, Tew DJ, Jenkins AL, Bottomley SP, Mackie EJ (1999) Thrombin, a survival factor for cultured myoblasts. J Biol Chem 274:9169–9174
Christensen EN, Mendelsohn ME (2006) Cyclic GMP-dependent protein kinase Ialpha inhibits thrombin receptor-mediated calcium mobilization in vascular smooth muscle cells. J Biol Chem 281(13):8409–8416
Debeir T, Benavides J, Vige X (1996) Dual effects of thrombin and a 14-amino acid peptide agonist of the thrombin receptor on septal cholinergic neurons. Brain Res 708:159–166
Even-Ram SC, Maoz M, Pokroy E, Reich R, Katz BZ, Gutwein P, Altevogt P, Bar-Shavit R (2001) Tumor cell invasion is promoted by activation of protease activated receptor-1 in cooperation with the alpha vbeta 5 integrin. J Biol Chem 276:10952–10962
Hu L, Lee M, Campbell W, Perez-Soler R, Karpatkin S (2004) Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis. Blood 104:2746–2751
Hua Y, Keep RF, Schallert T, Hoff JT, Xi G (2003) A thrombin inhibitor reduces brain edema, glioma mass and neurological deficits in a rat glioma model. Acta Neurochir Suppl 86:503–506
Hua Y, Tang L, Keep RF, Schallert T, Fewel M, Muraszko K, Hoff JT, Xi G (2005) The role of thrombin in gliomas. J Thromb Haemost 3:1–7
Hua Y, Tang LL, Fewel ME, Keep RF, Schallert T, Muraszko KM, Hoff JT, Xi GH (2005) Systemic use of argatroban reduces tumor mass, attenuates neurological deficits and prolongs survival time in rat glioma models. Acta Neurochir Suppl 95:403–406
Hua Y, Xi G, Keep RF, Wu J, Jiang Y, Hoff JT (2002) Plasminogen activator inhibitor-1 induction after experimental intracerebral hemorrhage. J Cereb Blood Flow Metab 22:55–61
Kaushal V, Kohli M, Dennis RA, Siegel ER, Chiles WW, Mukunyadzi P (2006) Thrombin receptor expression is upregulated in prostate cancer. Prostate 66:273–282
Maragoudakis ME, Tsopanoglou NE (2000) On the mechanism(s) of thrombin induced angiogenesis. Adv Exp Med Biol 476:47–55
Maragoudakis ME, Tsopanoglou NE (2004) Role of thrombin in angiogenesis: a rebuttal. J Thromb Haemost 2:841–842
Maragoudakis ME, Tsopanoglou NE, Andriopoulou P, Maragoudakis MM (2000) Effects of thrombin/thrombosis in angiogenesis and tumour progression. Matrix Biol 19:345–351 [Review]
Medrano EE, Cafferata EG, Larcher F (1987) Role of thrombin in the proliferative response of T-47D mammary tumor cells. Mitogenic action and pleiotropic modifications induced together with epidermal growth factor and insulin. Exp Cell Res 172:354–364
Nierodzik ML, Bain RM, Liu LX, Shivji M, Takeshita K, Karpatkin S (1996) Presence of the seven transmembrane thrombin receptor on human tumour cells: effect of activation on tumour adhesion to platelets and tumor tyrosine phosphorylation. Br J Haematol 92:452–457
Nierodzik ML, Chen K, Takeshita K, Li JJ, Huang YQ, Feng XS, D’Andrea MR, Andrade-Gordon P, Karpatkin S (1998) Protease-activated receptor 1 (PAR-1) is required and rate-limiting for thrombin-enhanced experimental pulmonary metastasis. Blood 92:3694–3700
Nierodzik ML, Kajumo F, Karpatkin S (1992) Effect of thrombin treatment of tumor cells on adhesion of tumor cells to platelets in vitro and tumor metastasis in vivo. Cancer Res 52:3267–3272
Nierodzik ML, Plotkin A, Kajumo F, Karpatkin S (1991) Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo. J Clin Invest 87:229–236
Suidan HS, Stone SR, Hemmings BA, Monard D (1992) Thrombin causes neurite retraction in neuronal cells through activation of cell surface receptors. Neuron 8:363–375
Wojtukiewicz MZ, Tang DG, Ben-Josef E, Renaud C, Walz DA, Honn KV (1995) Solid tumor cells express functional “tethered ligand” thrombin receptor. Cancer Res 55:698–704
Xi G, Hua Y, Keep RF, Hoff JT (2000) Induction of colligin may attenuate brain edema following intracerebral hemorrhage. Acta Neurochir Suppl 76:501–505
Xi G, Keep RF, Hoff JT (1998) Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg 89:991–996
Zacharski LR, Memoli VA, Morain WD, Schlaeppi JM, Rousseau SM (1995) Cellular localization of enzymatically active thrombin in intact human tissues by hirudin binding. Thromb Haemost 73:793–797
Zain J, Huang YQ, Feng X, Nierodzik ML, Li JJ, Karpatkin S (2000) Concentration-dependent dual effect of thrombin on impaired growth/apoptosis or mitogenesis in tumor cells. Blood 95:3133–3138
Acknowledgments
This study was supported by grants NS-017760, NS-039866, and NS-057539 from the National Institutes of Health (NIH) and 0840016 N from the American Heart Association (AHA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and AHA. Drs. Xie and Gong were supported by NSFC-30901549 and NSFC-30872675 from the China National Natural Science Foundation.
Conflict of InterestWe declare that we have no conflict of interest.
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Xie, Q., Xi, G., Gong, Y., Keep, R., Muraszko, K., Hua, Y. (2013). Protease Activated Receptor-1 and Brain Edema Formation in Glioma Models. In: Katayama, Y., Maeda, T., Kuroiwa, T. (eds) Brain Edema XV. Acta Neurochirurgica Supplement, vol 118. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1434-6_35
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