Neuroblastoma invasion strategies are regulated by the extracellular matrix

Cian Gavin, Nele Geerts, Brenton Cavanagh, Meagan Haynes, C. Patrick Reynolds, Daniela Loessner, Andrew J. Ewald, Olga Piskareva

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Neuroblastoma is a paediatric malignancy of the developing sympathetic nervous system. About half of the patients have metastatic disease at the time of diagnosis and a survival rate of less than 50%. Our understanding of the cellular processes promoting neuroblastoma metastases will be facilitated by the development of appropriate experimental models. In this study, we aimed to explore the invasion of neuroblastoma cells and organoids from patient‐derived xenografts (PDXs) grown embedded in 3D extracellular matrix (ECM) hydrogels by time‐lapse microscopy and quantitative image analysis. We found that the ECM composition influenced the growth, viability and local invasion of organoids. The ECM compositions induced distinct cell behaviours, with Matrigel being the preferred substratum for local organoid invasion. Organoid invasion was cell line‐ and PDX‐dependent. We identified six distinct phenotypes in PDX‐derived organoids. In contrast, NB cell lines were more phenotypically restricted in their invasion strategies, as organoids isolated from cell line‐derived xenografts displayed a broader range of phenotypes compared to clonal cell line clusters. The addition of FBS and bFGF induced more aggressive cell behaviour and a broader range of phenotypes. In contrast, the repression of the prognostic neuroblastoma marker, MYCN, resulted in less aggressive cell behaviour. The combination of PDX organoids, real‐time imaging and the novel 3D culture assays developed herein will enable rapid progress in elucidating the molecular mechanisms that control neuroblastoma invasion.

Original languageEnglish
Article number736
Pages (from-to)1-23
Number of pages23
JournalCancers
Volume13
Issue number4
DOIs
Publication statusPublished - 10 Feb 2021

Keywords

  • 3D invasion assay
  • Extracellular matrix environment (ECM)
  • Invasion phenotype
  • Neuroblastoma
  • Organoids

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