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Updated: Oct 22, 2025
Three-Dimensional In Vitro Biomimetic Model of Neuroblastoma Using Collagen-Based Scaffolds
Published on: July 9, 2021
Unraveling the extracellular matrix-tumor cell interactions to aid better targeted therapies for neuroblastoma
Rebeca Burgos-Panadero1, Souhaila H El Moukhtari2, Inmaculada Noguera3
1Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain; Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Abstract:
Treatment in children with high-risk neuroblastoma remains largely unsuccessful due to the development of metastases and drug resistance. The biological complexity of these tumors and their microenvironment represent one of the many challenges to face. Matrix glycoproteins such as vitronectin act as bridge elements between extracellular matrix and tumor cells and can promote tumor cell spreading. In this study, we established through a clinical cohort and preclinical models that the interaction of vitronectin and its ligands, such as αv integrins, are related to the stiffness of the extracellular matrix in high-risk neuroblastoma. These marked alterations found in the matrix led us to specifically target tumor cells within these altered matrices by employing nanomedicine and combination therapy. Loading the conventional cytotoxic drug etoposide into nanoparticles significantly increased its efficacy in neuroblastoma cells. We noted high synergy between etoposide and cilengitide, a high-affinity cyclic pentapeptide αv integrin antagonist. The results of this study highlight the need to characterize cell-extracellular matrix interactions, to improve patient care in high-risk neuroblastoma.
Insights
Targeting extracellular matrix interactions and using nanoparticle-delivered etoposide with cilengitide shows promise for treating high-risk neuroblastoma, a challenging childhood cancer.
Area of Science:
- Oncology
- Biochemistry
- Nanomedicine
Background:
- High-risk neuroblastoma in children is difficult to treat due to metastasis and drug resistance.
- Tumor microenvironment complexity and extracellular matrix (ECM) interactions pose significant challenges.
- Vitronectin, a matrix glycoprotein, can mediate tumor cell spreading by bridging ECM and tumor cells.
Purpose of the Study:
- To investigate the relationship between vitronectin-integrin interactions, ECM stiffness, and high-risk neuroblastoma.
- To evaluate the efficacy of targeting these interactions using nanomedicine and combination therapy.
Main Methods:
- Clinical cohort analysis and preclinical neuroblastoma models were used.
- Vitronectin-ligand interactions and ECM stiffness were assessed.
- Nanoparticle-encapsulated etoposide and cilengitide (an αv integrin antagonist) combination therapy was tested.
Main Results:
- Vitronectin-αv integrin interactions correlate with ECM stiffness in high-risk neuroblastoma.
- Etoposide loaded into nanoparticles demonstrated increased efficacy in neuroblastoma cells.
- High synergy was observed between etoposide and cilengitide.
Conclusions:
- Characterizing cell-ECM interactions is crucial for improving high-risk neuroblastoma treatment.
- Targeting vitronectin-integrin pathways with nanomedicine and combination therapy offers a promising therapeutic strategy.
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