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Demonstration of apoptosis in neuroblastoma and its relationship to tumour regression
H Koizumi1, M Wakisaka, K Nakada
1Second Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Japan.
Abstract:
The in vivo occurrence of apoptosis in neuroblastomas was investigated. Histologically, a number of tumour cells showed typical apoptotic changes, including cell shrinkage, condensed and fragmented nuclei, eosinophilic cytoplasm, and absence of the inflammatory response. These cells coincided closely with the so-called karyorrhectic cells. An electrophoretic DNA ladder, a functional hallmark of apoptosis, was demonstrated in four of six tumours, and DNA fragmentation was detected in situ by terminal deoxytransferase-mediated nick end-labelling in 26 of 35 tumour specimens (74%). The labelled cell counts ranged from 5 to 62 per 5000 tumour cells (mean +/- SD: 15.0 +/- 14.5). Immunoperoxidase staining revealed that an apoptosis-suppressing protein, bcl-2, was expressed abundantly in advanced-stage tumours, whereas it was absent from karyorrhectic-apoptotic cells. Several tumours with the potential for spontaneous regression were bcl-2-deficient. Immunostaining of the Fas receptor for apoptosis demonstrated that the tumour cells expressed this molecule on their cell surfaces. Our results provide evidence of apoptosis in neuroblastomas and suggest that bcl-2 and the Fas receptor may play a role in its regulatory mechanisms.
Insights
Apoptosis, programmed cell death, occurs in neuroblastomas. The apoptosis-suppressing protein bcl-2 and the Fas receptor are involved in regulating this process in these pediatric tumors.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Neuroblastomas are pediatric cancers with variable prognoses.
- Understanding cell death mechanisms like apoptosis is crucial for cancer research.
- The role of apoptosis regulators in neuroblastoma development requires further investigation.
Purpose of the Study:
- To investigate the occurrence and mechanisms of apoptosis in neuroblastoma tumors.
- To examine the expression of apoptosis-related proteins, specifically bcl-2 and Fas receptor, in neuroblastomas.
Main Methods:
- Histological examination of tumor tissues for apoptotic morphological changes.
- Electrophoretic DNA laddering to detect DNA fragmentation.
- In situ DNA fragmentation detection using terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNL).
- Immunoperoxidase staining for bcl-2 protein and Fas receptor expression.
Main Results:
- Typical apoptotic changes were observed in neuroblastoma cells.
- DNA fragmentation, a hallmark of apoptosis, was detected in 74% of tumor specimens.
- The apoptosis-suppressing protein bcl-2 was highly expressed in advanced-stage tumors and absent in apoptotic cells.
- Tumors with spontaneous regression potential were often bcl-2 deficient.
- Neuroblastoma cells expressed the Fas receptor on their surface.
Conclusions:
- Apoptosis occurs in neuroblastomas.
- The bcl-2 protein and Fas receptor are implicated in the regulation of apoptosis in neuroblastoma.
- These findings may offer insights into neuroblastoma behavior and potential therapeutic targets.