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Neuroblastoma invasion strategies are regulated by the extracellular matrix.

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journal contribution
posted on 26.03.2021, 13:49 by Cian Gavin, Nele Geerts, Brenton Cavanagh, Megan Haynes, C Patrick Reynolds, Daniela Loessner, Andrew J Ewald, Olga Piskareva
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.

Funding

Fulbright—HRB Health Impact Scholar Award 2018/19

National Children’s Research Centre (Project grant A/17/2)

Science Foundation Ireland (18/TIDA/6003)

RCSI Strategic Academic Recruitment (StAR) Programme

National Institutes of Health/National Cancer Institute (U01CA217846)

Alex’s Lemonade Stand Foundation for the COG Childhood Cancer Repository

National Institutes of Health/National Cancer Institute (RO1 CA221957)

History

Associated research data files

Supplementary materials (including data) available at https://doi.org/10.3390/cancers13040736

Comments

The original article is available at https://www.mdpi.com

Published Citation

Gavin C, Geerts N, Cavanagh B, Haynes M, Reynolds CP, Loessner D, Ewald AJ, Piskareva O. Neuroblastoma invasion strategies are regulated by the extracellular matrix. Cancers (Basel). 2021;13(4):736

Publication Date

10 February 2021

PubMed ID

33578855

Department/Unit

  • Anatomy and Regenerative Medicine
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Cancer
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation

Publisher

MDPI AG

Version

  • Published Version (Version of Record)

Licence

Exports

Royal College of Surgeons in Ireland

Licence

Exports