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Updated: Sep 18, 2025
05:20
Zebrafish Model of Neuroblastoma Metastasis
Published on: March 14, 2021
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Extracellular Matrix Topography Drives Adrenergic to Mesenchymal Transition in Neuroblastoma
Antonios Chronopoulos1, Chandra Kaladhar Vemula1, Vic Zamloot1
1Cancer and Blood Disease Institute, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, California, 90027, USA.
Advanced Materials (Deerfield Beach, Fla.)
|June 25, 2025
Summary
The extracellular matrix (ECM) topography drives neuroblastoma (NB) cell transition to a mesenchymal (MES) identity, promoting metastasis and therapy resistance. Targeting ECM topography may offer new therapeutic strategies for high-risk NB.
Area of Science:
- Oncology
- Biomaterials Science
- Cell Biology
Background:
- Neuroblastoma (NB) is a common pediatric cancer characterized by intra-tumoral heterogeneity.
- NB cells exist in adrenergic (ADRN) and mesenchymal (MES) states, with MES cells linked to metastasis and treatment resistance.
- The extracellular matrix (ECM) within the tumor microenvironment (TME) influences cancer progression.
Purpose of the Study:
- To investigate the role of ECM topography in driving the ADRN-to-MES transition (AMT) in neuroblastoma.
- To elucidate the molecular mechanisms underlying ECM-driven AMT.
- To explore potential TME-targeted therapeutic strategies for high-risk NB.
Main Methods:
- Utilized nano-fabricated biomaterials mimicking aligned ECM topography.
- Analyzed transcriptional and epigenetic changes in NB cells cultured on biomaterials.
- Assessed phenotypic changes related to MES identity.
- Investigated the involvement of Rho-associated kinase and YAP signaling pathways.
Main Results:
- High-risk NB tumors exhibit more topographically aligned ECM fibers than low-risk tumors.
- Mimicking aligned ECM topography induced AMT, enhancing MES features.
- ECM topography triggered transcriptional, epigenetic, and signaling pathway alterations (Rho-kinase, YAP).
- ECM topography was identified as a driver of NB cell reprogramming.
Conclusions:
- ECM topography is a novel mechanism driving AMT in neuroblastoma.
- Targeting ECM topography and associated signaling pathways presents a potential therapeutic strategy.
- Suppression of MES cells via TME modulation could improve clinical outcomes in NB.
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