Apoptosis in favourable neuroblastomas is not dependent on Fas (CD95/APO-1) expression but on activated caspase 3 (CPP32)

• Published in: The Journal of pathology 1999-11, Vol.189 (3), p.410-415
• Main Authors: Koizumi, Hirotaka, Ohkawa, Ikuo, Tsukahara, Toshifumi, Momoi, Takashi, Nakada, Koonosuke, Uchikoshi, Toshiyuki
• Format: Article
• Language: English
• Subjects: apoptosis; Apoptosis - physiology; Biological and medical sciences; Caspase 3; Caspases - metabolism; CPP32; Enzyme Activation; Enzyme Precursors - metabolism; Fas; Fas ligand; fas Receptor - metabolism; Humans; Immunoenzyme Techniques; Infant; Ligands; Medical sciences; Neuroblastoma - enzymology; Neuroblastoma - metabolism; Neuroblastoma - physiopathology; neuroblastomas; Neurology; Tumors of the nervous system. Phacomatoses; tumour regression
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/(SICI)1096-9896(199911)189:3<410::AID-PATH453>3.0.CO;2-H

The mechanisms of apoptosis in neuroblastomas have been investigated by examining 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 levels of expression of FasL and pro‐caspase 3 were noted in 30 and 29 of 42 tumours, respectively (∼70 per cent). Overexpression of pro‐caspase 3, but not FasL, correlated significantly with a younger age and low tumour stage. Western blot analysis of ten neuroblastomas confirmed the lack of Fas expression and the presence of strong FasL expression in all samples and pro‐caspase 3 expression in five 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 localized in apoptotic tumour cells. Combined together, our results suggest that caspase 3, activated via a Fas‐independent pathway, may play important roles in apoptosis, suppression of growth, and, in some cases, regression of favourable neuroblastomas. Copyright © 1999 John Wiley & Sons, Ltd.