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

Fas (APO-1/CD95/TNFRSF6) is a member of the tumor necrosis/nerve growth fac tor receptor family that signals apoptotic cell death in sensitive cells. E xpression of Fas and its agonistic ligand (FasL/TNFSF6) was investigated in ex vivo pediatric brain tumor specimens of various histologic types. Fas e xpression was identified in all of the 18 tumors analyzed by flow cytometry and immunohistochemistry. FasL expression was identified in most of the 13 tumors analyzed by both Western analysis and immunohistochemistry. Nine of these tumor specimens were treated with either the agonistic anti-Fas anti body (APO-1) in combination with protein A or FasL in shortterm cytotoxicit y assays. Sensitivity to apoptosis induced by the topoisomerase II inhibito r, etoposide, was also assessed. Despite the presence of Fas, all the speci mens analyzed demonstrated a high degree of resistance to Fas-mediated apop tosis. These 9 specimens also showed a high degree of resistance to etoposi de. Only 2 of the 9 specimens were susceptible to etoposide-induced cell de ath, whereas only 3 were sensitive to Fas-mediated apoptosis. One brain tum or was sensitive to both Fas ligation and etoposide treatment. This contras ted with the high degree of susceptibility to both etoposide- and Fas-induc ed apoptosis observed in the reference jurkat cell line. The results sugges t that Fas expression may be a general feature of tumors of the CNS and tha t a significant degree of resistance to Fas-mediated apoptosis may exist in ex vivo pediatric brain tumor specimens.