Journal
CANCER LETTERS
Volume 375, Issue 2, Pages 384-389Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.02.046
Keywords
Paediatric cancer; Neuroblastoma; Tumour microenvironment; Tumour stroma; Patient-derived xenograft (PDX); Metastasis
Categories
Funding
- Swedish Cancer Society
- Swedish Childhood Cancer Foundation
- Swedish Research Council, VINNOVA
- SSF Strategic Center for Translational Cancer Research-CREATE Health
- Strategic Cancer Research Program BioCARE
- Crafoord Foundation
- Jeanssons Stiftelser
- Berth von Kantzows Stiftelse
- Royal Physiographic Society in Lund
- Gunnar Nilsson Cancer Foundation
- Gyllenstierna Krapperup's Foundation
- Ollie och Elof Ericssons Stiftelser
- Region Skane
- Skane University Hospital
- FIS contract [PI14/01008]
- RTICC [RD12/0036/0027]
- ISCIII & FEDER (European Regional Development Fund), Spain
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Treatment of high-risk childhood neuroblastoma is a clinical challenge which has been 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. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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