Apoptosis in favourable neuroblastomas is not dependent on Fas (CD95/APO-1) expression but on activated caspase 3 (CPP32).
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 (approximately 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.
Koizumi
H
H
Department of Pathology, St Marianna University School of Medicine, Kawasaki, Japan. hiro@marianna-u.ac.jp
Ohkawa
I
I
Tsukahara
T
T
Momoi
T
T
Nakada
K
K
Uchikoshi
T
T
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008024:Ligands; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D019014:fas Receptor / Q000378:metabolism*
D004792:Enzyme Precursors; D008024:Ligands; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases