Related Experiment Video
Updated: Aug 5, 2025
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Evaluating the RIST Molecular-Targeted Regimen in a Three-Dimensional Neuroblastoma Spheroid Cell Culture Model
Carina Kaess1, Marie Matthes1, Jonas Gross1
1Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital of Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany.
Background:
The outcome for patients with high-risk neuroblastoma remains poor and novel treatment strategies are urgently needed. The RIST protocol represents a novel metronomic and multimodal treatment strategy for high-risk neuroblastoma combining molecular-targeted drugs as 'pre-treatment' with a conventional chemotherapy backbone, currently evaluated in a phase II clinical trial. For preclinical drug testing, cancer cell growth as spheroid compared to mo-nolayer cultures is of advantage since it reproduces a wide range of tumor characteristics, including the three-dimensional architecture and cancer stem cell (CSC) properties. The objective of this study was to establish a neuroblastoma spheroid model for the rigorous assessment of the RIST treatment protocol.
Methods:
Evaluation of CSC marker expression was performed by mRNA and protein analysis and spheroid viability by luminescence-based assays. Aberrant expression of RNA-binding protein La in neuroblastoma was assessed by tissue microarray analysis and patients' data mining.
Results:
Spheroid cultures showed increased expression of a subgroup of CSC-like markers (CXCR4, NANOG and BMI) and higher Thr389 phosphorylation of the neuroblastoma-associated RNA-binding protein La when compared to monolayer cultures. Molecular-targeted 'pre-treatment' of spheroids decreased neoplastic signaling and CSC marker expression.
Conclusions:
The RIST treatment protocol efficiently reduced the viability of neuroblastoma spheroids characterized by advanced CSC properties.
Insights
A new neuroblastoma spheroid model effectively assessed the RIST protocol, a novel treatment strategy. This model demonstrated that RIST reduces cancer stem cell (CSC) properties and viability in high-risk neuroblastoma.
Area of Science:
- Oncology
- Cancer Research
- Drug Development
Background:
- High-risk neuroblastoma has a poor prognosis, necessitating novel therapeutic approaches.
- The RIST protocol combines targeted drugs and chemotherapy for high-risk neuroblastoma.
- Spheroid cultures better mimic tumor characteristics than monolayer cultures for preclinical testing.
Purpose of the Study:
- To establish a neuroblastoma spheroid model for evaluating the RIST treatment protocol.
- To assess the RIST protocol's efficacy in a preclinical setting.
Main Methods:
- Neuroblastoma spheroid and monolayer cultures were established.
- Cancer stem cell (CSC) marker expression was analyzed via mRNA and protein assays.
- Spheroid viability was measured using luminescence assays; RNA-binding protein La expression was assessed.
Main Results:
- Spheroids exhibited higher expression of CSC markers (CXCR4, NANOG, BMI) and RNA-binding protein La phosphorylation compared to monolayers.
- Targeted pre-treatment within the RIST protocol reduced neoplastic signaling and CSC marker expression.
- The RIST protocol significantly decreased the viability of neuroblastoma spheroids.
Conclusions:
- The established neuroblastoma spheroid model is suitable for rigorous assessment of novel treatment strategies like RIST.
- The RIST protocol demonstrates efficacy in reducing the viability of neuroblastoma spheroids with advanced CSC properties.
More Related Videos
07:48Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
13:19Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024