Neuroblastoma patient-derived xenograft cells cultured in stem-cell promoting medium retain tumorigenic and metastatic capacities but differentiate in serum
(2017) In Scientific Reports 7(1).- Abstract
Cultured cancer cells serve as important models for preclinical testing of anti-cancer compounds. However, the optimal conditions for retaining original tumor features during in vitro culturing of cancer cells have not been investigated in detail. Here we show that serum-free conditions are critical for maintaining an immature phenotype of neuroblastoma cells isolated from orthotopic patient-derived xenografts (PDXs). PDX cells could be grown either as spheres or adherent on laminin in serum-free conditions with retained patient-specific genomic aberrations as well as tumorigenic and metastatic capabilities. However, addition of serum led to morphological changes, neuronal differentiation and reduced cell proliferation. The epidermal... (More)
Cultured cancer cells serve as important models for preclinical testing of anti-cancer compounds. However, the optimal conditions for retaining original tumor features during in vitro culturing of cancer cells have not been investigated in detail. Here we show that serum-free conditions are critical for maintaining an immature phenotype of neuroblastoma cells isolated from orthotopic patient-derived xenografts (PDXs). PDX cells could be grown either as spheres or adherent on laminin in serum-free conditions with retained patient-specific genomic aberrations as well as tumorigenic and metastatic capabilities. However, addition of serum led to morphological changes, neuronal differentiation and reduced cell proliferation. The epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were central for PDX cell proliferation and MYCN expression, and also hindered the serum-induced differentiation. Although serum induced a robust expression of neurotrophin receptors, stimulation with their cognate ligands did not induce further sympathetic differentiation, which likely reflects a block in PDX cell differentiation capacity coupled to their tumor genotype. Finally, PDX cells cultured as spheres or adherent on laminin responded similarly to various cytotoxic drugs, suggesting that both conditions are suitable in vitro screening models for neuroblastoma-targeting compounds.
(Less)
- author
- Persson, Camilla U. LU ; Von Stedingk, Kristoffer LU ; Bexell, Daniel LU ; Merselius, My LU ; Braekeveldt, Noémie LU ; Gisselsson, David LU ; Arsenian-Henriksson, Marie ; Påhlman, Sven LU and Wigerup, Caroline LU
- organization
-
- Molecular oncology (research group)
- Childhood Cancer Research Unit (research group)
- Molecular Pediatric Oncology (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Division of Translational Cancer Research
- Pathways of cancer cell evolution (research group)
- publishing date
- 2017-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 7
- issue
- 1
- article number
- 10274
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85028667225
- pmid:28860499
- wos:000408781200133
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-017-09662-8
- language
- English
- LU publication?
- yes
- id
- c16c4726-5901-4ba1-82b0-5a986685fda4
- date added to LUP
- 2017-09-25 13:55:59
- date last changed
- 2024-05-12 21:17:22
@article{c16c4726-5901-4ba1-82b0-5a986685fda4,
abstract = {{<p>Cultured cancer cells serve as important models for preclinical testing of anti-cancer compounds. However, the optimal conditions for retaining original tumor features during in vitro culturing of cancer cells have not been investigated in detail. Here we show that serum-free conditions are critical for maintaining an immature phenotype of neuroblastoma cells isolated from orthotopic patient-derived xenografts (PDXs). PDX cells could be grown either as spheres or adherent on laminin in serum-free conditions with retained patient-specific genomic aberrations as well as tumorigenic and metastatic capabilities. However, addition of serum led to morphological changes, neuronal differentiation and reduced cell proliferation. The epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were central for PDX cell proliferation and MYCN expression, and also hindered the serum-induced differentiation. Although serum induced a robust expression of neurotrophin receptors, stimulation with their cognate ligands did not induce further sympathetic differentiation, which likely reflects a block in PDX cell differentiation capacity coupled to their tumor genotype. Finally, PDX cells cultured as spheres or adherent on laminin responded similarly to various cytotoxic drugs, suggesting that both conditions are suitable in vitro screening models for neuroblastoma-targeting compounds.</p>}},
author = {{Persson, Camilla U. and Von Stedingk, Kristoffer and Bexell, Daniel and Merselius, My and Braekeveldt, Noémie and Gisselsson, David and Arsenian-Henriksson, Marie and Påhlman, Sven and Wigerup, Caroline}},
issn = {{2045-2322}},
language = {{eng}},
month = {{12}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Neuroblastoma patient-derived xenograft cells cultured in stem-cell promoting medium retain tumorigenic and metastatic capacities but differentiate in serum}},
url = {{http://dx.doi.org/10.1038/s41598-017-09662-8}},
doi = {{10.1038/s41598-017-09662-8}},
volume = {{7}},
year = {{2017}},
}