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

Braekeveldt, Noémie LU ; Wigerup, Caroline LU ; Tadeo, Irene; Beckman, Siv LU ; Sandén, Caroline LU ; Jönsson, Jimmie; Erjefält, Jonas S LU ; Berbegall, Ana P; Börjesson, Anna LU and Backman, Torbjörn LU , et al. (2016) In Cancer Letters 375(2). p.384-389
Abstract

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... (More)

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.

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publication status
published
subject
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Cancer Letters
volume
375
issue
2
pages
384 - 389
publisher
Elsevier
external identifiers
  • Scopus:84961789680
ISSN
1872-7980
DOI
10.1016/j.canlet.2016.02.046
language
English
LU publication?
yes
id
f8acfb85-034f-4c5d-bc32-d62da958b813
date added to LUP
2016-04-12 15:51:49
date last changed
2016-11-28 07:37:39
@misc{f8acfb85-034f-4c5d-bc32-d62da958b813,
  abstract     = {<p>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.</p>},
  author       = {Braekeveldt, Noémie and Wigerup, Caroline and Tadeo, Irene and Beckman, Siv and Sandén, Caroline and Jönsson, Jimmie and Erjefält, Jonas S and Berbegall, Ana P and Börjesson, Anna and Backman, Torbjörn and Øra, Ingrid and Navarro, Samuel and Noguera, Rosa and Gisselsson, David and Påhlman, Sven and Bexell, Daniel},
  issn         = {1872-7980},
  language     = {eng},
  number       = {2},
  pages        = {384--389},
  publisher    = {ARRAY(0xaabf090)},
  series       = {Cancer Letters},
  title        = {Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours},
  url          = {http://dx.doi.org/10.1016/j.canlet.2016.02.046},
  volume       = {375},
  year         = {2016},
}