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Neuro-Oncology 2001 3(4):229-240; doi:10.1093/neuonc/3.4.229
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© 2001 by the Society forNeuro-Oncology

Ex vivo pediatric brain tumors express Fas (CD95) and FasL (CD95L) andare resistant to apoptosis induction

Christopher D. Riffkin, Amy Z. Gray, Christine J. Hawkins, C.W. Chow and David M. Ashley2

Department of Hematology and Oncology (C.D.R., A.Z.G.,C.J.H., D.M.A) and Department of Anatomical Pathology(C.W.C.), Royal Children's Hospital, Flemington Road, Parkville 3052,Melbourne, Victoria, Australia

2 Address correspondence and reprint requests to David M. Ashley, Department ofHaematology and Oncology, Royal Children's Hospital, Flemington Road,Parkville 3052, Melbourne, Victoria, Australia.


   Abstract

Fas (APO-1/CD95/TNFRSF6) is a member of the tumor necrosis/nerve growthfactor receptor family that signals apoptotic cell death in sensitive cells.Expression of Fas and its agonistic ligand (FasL/TNFSF6) was investigated inex vivo pediatric brain tumor specimens of various histologic types. Fasexpression was identified in all of the 18 tumors analyzed by flow cytometryand immunohistochemistry. FasL expression was identified in most of the 13tumors analyzed by both Western analysis and immunohistochemistry. Nine ofthese tumor specimens were treated with either the agonistic anti-Fas antibody(APO-1) in combination with protein A or FasL in short-term cytotoxicityassays. Sensitivity to apoptosis induced by the topoisomerase II inhibitor,etoposide, was also assessed. Despite the presence of Fas, all the specimensanalyzed demonstrated a high degree of resistance to Fas-mediated apoptosis.These 9 specimens also showed a high degree of resistance to etoposide. Only 2of the 9 specimens were susceptible to etoposide-induced cell death, whereasonly 3 were sensitive to Fas-mediated apoptosis. One brain tumor was sensitiveto both Fas ligation and etoposide treatment. This contrasted with the highdegree of susceptibility to both etoposide- and Fas-induced apoptosis observedin the reference Jurkat cell line. The results suggest that Fas expression maybe a general feature of tumors of the CNS and that a significant degree ofresistance to Fas-mediated apoptosis may exist in ex vivo pediatric braintumor specimens.

Received January 10, 2001; Accepted April 2, 2001


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