Abstract
Development of new therapies for glioblastoma requires animal models that mimic the biological characteristics of human brain tumors. On the other hand, potential antitumoral effects of a new therapeutic strategy are often established by evaluation of tumor cells apoptosis. Caspases are key mediators in the regulation and execution of apoptosis. Caspase-9 is activated during the intrinsic pathway downstream of mitochondria while caspase-3 is an effector caspase that initiates degradation of the cell in the final stages of apoptosis. Bax is a pro-apoptotic member of the Bcl-2 family that play key roles in the regulation of intrinsic apoptotic signaling. In the present study we investigated the immunohistochemical distribution of caspase 3, 9 and Bax in intracranial U87 glioblastoma xenograft. Immunohistochemistry showed that the glioblastoma xenografts contain cells positive for caspase-3, caspase-9, and Bax.
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Bodey B, Bodey V, Siegel SE, Nasir A, Coppola D, Hakam A, Kaiser HE (2004) Immunocytochemical detection of members of the caspase cascade of apoptosis in high-grade astrocytomas. In Vivo 18:593–602
Candolfi M, Curtin JF, Nichols WS, Muhammad AG, King GD, Pluhar GE, McNiel EA, Ohlfest JR, Freese AB, Moore PF, Lerner J, Lowenstein PR, Castro MG (2007) Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression. J Neurooncol 85:133–148
Cartron PF, Oliver L, Martin S, Moreau C, LeCabellec MT, Jezequel P, Meflah K, Vallette FM (2002) The expression of a new variant of the pro-apoptotic molecule Bax, Baxpsi, is correlated with an increased survival of glioblastoma multiforme patients. Hum Mol Genet 11:675–687
Chen GG, Chak EC, Chun YS, Lam IK, Sin FL, Leung BC, Ng HK, Poon WS (2003) Glioma apoptosis induced by macrophages involves both death receptor-dependent and independent pathways. J Lab Clin Med 141:190–199
Farin A, Suzuki SO, Weiker M, Goldman JE, Bruce JN, Canoll P (2006) Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis. Glia 53:799–808
Gdynia G, Grund K, Eckert A, Böck BC, Funke B, Macher-Goeppinger S, Sieber S, Herold-Mende C, Wiestler B, Wiestler OD, Roth W (2007) Basal caspase activity promotes migration and invasiveness in glioblastoma cells. Mol Cancer Res 5:1232–1240
Guillamo JS, Lisovoski F, Christov C, Le Guérinel C, Defer GL, Peschanski M, Lefrançois T (2001) Migration pathways of human glioblastoma cells xenografted into the immunosuppressed rat brain. J Neurooncol 52:205–215
Karmakar S, Banik NL, Patel SJ, Ray SK (2007a) Combination of all-trans retinoic acid and taxol regressed glioblastoma T98G xenografts in nude mice. Apoptosis 12:2077–2087
Karmakar S, Banik NL, Ray SK (2007b) Curcumin suppressed anti-apoptotic signals and activated cysteine proteases for apoptosis in human malignant glioblastoma U87MG cells. Neurochem Res 32:2103–2113
Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61:215–225
Lal B, Xia S, Abounader R, Laterra J (2005) Targeting the c-Met pathway potentiates glioblastoma responses to gamma-radiation. Clin Cancer Res 11:4479–4486
Logue SE, Martin SJ (2008) Caspase activation cascades in apoptosis. Biochem Soc Trans 36:1–9
Martens T, Schmidt NO, Eckerich C, Fillbrandt R, Merchant M, Schwall R, Westphal M, Lamszus K (2006) A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo. Clin Cancer Res 12:6144–6152
Martin S, Toquet C, Oliver L, Cartron PF, Perrin P, Meflah K, Cuillère P, Vallette FM (2001) Expression of bcl-2, bax and bcl-xl in human gliomas: a re-appraisal. J Neurooncol 52:129–139
Mizoguchi M, Inamura T, Shono T, Ikezaki K, Inoha S, Ohgami S, Fukui M (2000) A comparative study of apoptosis and proliferation in germinoma and glioblastoma. Neuro Oncol 2:96–102
Nestor SL (2008) Techniques in neuropathology. In: Bancroft JD, Gamble M (eds) Theory and practice of histological techniques, 6th edn. Churchill Livingstone Elsevier, Philadelphia, pp 365–403
Pathak S, Nemeth MA, Multani AS (1998) Human tumor xenografts in nude mice are not always of human origin: a warning signal. Cancer 83:1891–1893
Pilkington GJ, Parker K (2007) Models for CNS malignancies. In: Alison MR (ed) The cancer handbook, 2nd edn. John Wiley & Sons, Chichester, England, UK, pp 1176–1190
Ray SK, Patel SJ, Welsh CT, Wilford GG, Hogan EL, Banik NL (2002) Molecular evidence of apoptotic death in malignant brain tumors including glioblastoma multiforme: upregulation of calpain and caspase-3. J Neurosci Res 69:197–206
Scott TJ (1971) A rapid silver impregnation technique for oligodendrocytes, microglia, and astrocytes. J Clin Pathol 24:578–580
Strojnik T, Kavalar R, Lah TT (2006) Experimental model and immunohistochemical analyses of U87 human glioblastoma cell xenografts in immunosuppressed rat brains. Anticancer Res 26:2887–2900
Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9:231–241
Weppler SA, Krause M, Zyromska A, Lambin P, Baumann M, Wouters BG (2007) Response of U87 glioma xenografts treated with concurrent rapamycin and fractionated radiotherapy: possible role for thrombosis. Radiother Oncol 82:96–104
Yang L, Cao Z, Yan H, Wood WC (2003) Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: implication for cancer specific therapy. Cancer Res 63:6815–6824
Yoo NJ, Kim HS, Kim SY, Park WS, Kim SH, Lee JY, Lee SH (2002) Stomach cancer highly expresses both initiator and effector caspases; an immunohistochemical study. APMIS 110:825–832
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This work was supported by Romanian CEEX Programme, Project No. 176/2006.
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Zarnescu, O., Brehar, F.M., Chivu, M. et al. Immunohistochemical localization of caspase-3, caspase-9 and Bax in U87 glioblastoma xenografts. J Mol Hist 39, 561–569 (2008). https://doi.org/10.1007/s10735-008-9196-8
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DOI: https://doi.org/10.1007/s10735-008-9196-8