Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours
Författare
Summary, in 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.
Avdelning/ar
- Molekylär barnonkologi
- Avdelningen för translationell cancerforskning
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Institutionen för experimentell medicinsk vetenskap
- Pediatrik, Lund
- Avdelningen för klinisk genetik
Publiceringsår
2016
Språk
Engelska
Sidor
384-389
Publikation/Tidskrift/Serie
Cancer Letters
Volym
375
Issue
2
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Cancer and Oncology
Status
Published
Forskningsgrupp
- Molecular Pediatric Oncology
ISBN/ISSN/Övrigt
- ISSN: 1872-7980