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Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours

Author:
  • Noémie Braekeveldt
  • Caroline Wigerup
  • Irene Tadeo
  • Siv Beckman
  • Caroline Sandén
  • Jimmie Jönsson
  • Jonas S Erjefält
  • Ana P Berbegall
  • Anna Börjesson
  • Torbjörn Backman
  • Ingrid Øra
  • Samuel Navarro
  • Rosa Noguera
  • David Gisselsson
  • Sven Påhlman
  • Daniel Bexell
Publishing year: 2016
Language: English
Pages: 384-389
Publication/Series: Cancer Letters
Volume: 375
Issue: 2
Document type: Journal article
Publisher: Elsevier

Abstract english

Treatment of high-risk childhood neuroblastoma is a clinical challenge hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient-derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich blood and lymphatic vascularisation, pericyte coverage, high numbers of cancer-associated fibroblasts, tumour-associated macrophages, and extracellular matrix components. Patient-derived tumour endothelial cells occasionally formed blood vessels in PDXs; however, tumour stroma was, overall, of murine origin. Lymphoid cells and lymphatic endothelial cells were found in athymic nude mice but not in NSG mice; thus, the choice of mouse strain dictates tumour microenvironmental components. The murine tumour microenvironment of orthotopic neuroblastoma PDXs reflects important hallmarks of aggressive and metastatic clinical neuroblastomas. Neuroblastoma PDXs are clinically relevant models for preclinical drug testing.

Keywords

  • Cancer and Oncology

Other

Published
  • Molecular Pediatric Oncology
  • ISSN: 1872-7980
Sven Påhlman
E-mail: sven.pahlman [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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