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Updated: Aug 19, 2026
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Published on: February 7, 2025
A proteomic investigation into etoposide chemo-resistance of neuroblastoma cell lines
Andrea Urbani1, Julia Poland, Sergio Bernardini
1Centro Studi sull'Invecchiamento (Ce.S.I.), Fondazione Università G. D'Annunzio, Chieti, Italy. a.urbani@unich.it
Abstract:
Neuroblastoma, one of the most common pediatric solid tumors, originates from the peripheral sympathetic nervous system and is responsible for approximately 15% of all childhood cancer deaths. Among the several antineoplastic drugs used in neuroblastoma chemotherapeutic protocols, topoisomerase inhibitors (i.e., etoposide) represent the most commonly used. Several resistance mechanisms limit the clinical success of topoisomerase-targeting drugs, mainly reducing the ability of neoplastic cells to start programmed cell death when exposed to antineoplastic drugs. The aim of this study was to determine, by means of proteomics, potential markers of etoposide resistance in human neuroblastoma cell lines as well as to investigate protein levels and modifications possibly involved in the onset of resistance. The etoposide resistant clone showed overexpression of the following proteins: peroxiredoxin 1, beta-galactoside soluble lectin binding protein, vimentin (three protein spots), heat shock 27 kDa protein (two protein spots) and heterogeneous nuclear ribonucleoprotein K. In addition, we also found down-regulation of dUTP pyrophosphatase. This investigation might represent a first step towards the development of novel prognostic markers of neuroblastoma chemotherapy.
Insights
Researchers identified protein markers for etoposide resistance in neuroblastoma, a common childhood cancer. Proteomics revealed specific protein changes, offering potential for new prognostic markers in chemotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Neuroblastoma is a frequent pediatric solid tumor originating from the peripheral sympathetic nervous system.
- It accounts for a significant portion of childhood cancer mortality.
- Topoisomerase inhibitors, like etoposide, are primary chemotherapeutic agents, but drug resistance limits their efficacy by hindering cancer cell death.
Purpose of the Study:
- To identify potential protein markers associated with etoposide resistance in human neuroblastoma cell lines using proteomics.
- To investigate protein level alterations and modifications involved in the development of etoposide resistance.
Main Methods:
- Proteomic analysis was employed to compare protein expression profiles between etoposide-sensitive and etoposide-resistant neuroblastoma cell lines.
- Quantitative analysis of protein spots and identification of differentially expressed proteins.
Main Results:
- Overexpression of peroxiredoxin 1, beta-galactoside soluble lectin binding protein, vimentin, heat shock 27 kDa protein, and heterogeneous nuclear ribonucleoprotein K was observed in the resistant clone.
- Down-regulation of dUTP pyrophosphatase was also detected in the etoposide-resistant neuroblastoma cells.
- Specific protein modifications and altered expression levels were identified as potential contributors to etoposide resistance.
Conclusions:
- The identified proteins (peroxiredoxin 1, beta-galactoside soluble lectin binding protein, vimentin, heat shock 27 kDa protein, heterogeneous nuclear ribonucleoprotein K, and dUTP pyrophosphatase) may serve as potential biomarkers for etoposide resistance in neuroblastoma.
- This proteomic investigation provides a foundation for developing novel prognostic markers to guide neuroblastoma chemotherapy.
- Understanding these resistance mechanisms can inform future therapeutic strategies to improve treatment outcomes for pediatric neuroblastoma patients.