Apoptosis in favourable neuroblastomas is not dependent on Fas (CD95/APO-1) expression but on activated caspase 3 (CCP32)

The mechanisms of apoptosis in neuroblastomas have been investigated by exa mining the expression profiles of Fas, Fas ligand (FasL), and caspase 3 in 42 primary tumour tissues. Immunohistochemically, no or weak Fas expression was detected in 25 out of 29 neuroblastomas (86 per cent), whereas high le vels of expression of Fast and pro-caspase 3 were noted in 30 and 29 of 42 tumors, respectively (similar to 70 per cent). Overexpression of pro-caspas e 3, but not FasL, correlated significantly with a younger age and low tumo ur stage. Western blot analysis of ten neuroblastomas confirmed the lack of Fas expression and the presence of strong FasL expression in all samples a nd pro-caspase 3 expression in live tumours, of which four belonged to the favourable type. These favourable tumours also showed vigorous Asp-Glu-Val- Asp (DEVD) hydrolytic, or caspase 3-like activities, while the unfavourable : tumour lacked such activity. Moreover, immunostaining for the p17 subunit of the caspase 3 heterodimer showed that active caspase 3 was mainly local ized in apoptotic tumour cells. Combined together, our results suggest that caspase 3, activated via a Fas-independent pathway, may play important rol es in apoptosis, suppression of growth, and, in some cases, regression of f avourable neuroblastomas. Copyright (C) 1999 John Wiley & Sons, Ltd.