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Caspase 3 and 8 deficiency in human neuroblastoma
Achille Iolascon1, Adriana Borriello, Lucia Giordani
1Institute of Pediatrics, University of Foggia, Foggia, Italy.
Abstract:
An altered apoptotic response represents a pivotal feature of cancer and is involved in cancerogenesis and resistance to chemotherapy. So far, however, only a few studies have been devoted to survey caspase content in malignant cell lines and primary tumor specimens. In this report, we investigated the expression of two pivotal caspases, 3 and 8, in 63 neuroblastoma specimens by three complementary techniques (i.e., reverse transcriptase polymerase chain reaction, immunoblotting, and immunohistochemistry). We confirmed the frequent absence of caspase 8 expression. Moreover and most important, we demonstrated, for the first time to our knowledge, that a significant percentage of neuroblastomas lack caspase 3 mRNA and protein. Both caspase alterations do not show any correlation with tumor stage and MYCN status. Immunohistochemistry showed a large number of caspase-negative cell islets also present in positive samples. Our findings suggest that the absence of caspases might play an important role in neuroblastoma development and resistance to apoptosis-based treatments.
Insights
Neuroblastomas frequently lack caspase 8 and, importantly, caspase 3 expression. This absence of caspases may drive neuroblastoma development and chemotherapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Altered apoptosis is key in cancer development and treatment resistance.
- Caspase expression in malignant cells and tumors is understudied.
- Neuroblastoma is a pediatric cancer where apoptosis plays a critical role.
Purpose of the Study:
- To investigate the expression of caspases 3 and 8 in neuroblastoma.
- To determine the correlation between caspase expression and tumor characteristics.
- To explore the implications of caspase absence in neuroblastoma.
Main Methods:
- Analysis of 63 neuroblastoma specimens.
- Utilized reverse transcriptase polymerase chain reaction (RT-PCR) for mRNA detection.
- Employed immunoblotting and immunohistochemistry for protein analysis.
Main Results:
- Confirmed frequent absence of caspase 8 expression in neuroblastomas.
- Demonstrated for the first time that a significant percentage of neuroblastomas lack caspase 3 mRNA and protein.
- Observed no correlation between caspase alterations and tumor stage or MYCN status.
- Identified caspase-negative cell islets within positive samples via immunohistochemistry.
Conclusions:
- Absence of caspases 3 and 8 is common in neuroblastoma.
- Caspase deficiency may contribute to neuroblastoma pathogenesis.
- Lack of caspases could indicate resistance to apoptosis-based therapies.