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Title: Stem cell media culture of melanoma results in the induction of a nonrepresentative neural expression profile.
Austin Authors: Anaka, Matthew;Freyer, Claudia;Gedye, Craig;Caballero, Otavia;Davis, Ian D;Behren, Andreas;Cebon, Jonathan S 
Affiliation: Cancer Immuno-biology Lab, Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Melbourne, Victoria, Australia
Issue Date: 1-Feb-2012
Publication information: Stem Cells (dayton, Ohio); 30(2): 336-43
Abstract: The ability of cell lines to accurately represent cancer is a major concern in preclinical research. Culture of glioma cells as neurospheres in stem cell media (SCM) has been shown to better represent the genotype and phenotype of primary glioblastoma in comparison to serum cell lines. Despite the use of neurosphere-like models of many malignancies, there has been no robust analysis of whether other cancers benefit from a more representative phenotype and genotype when cultured in SCM. We analyzed the growth properties, transcriptional profile, and genotype of melanoma cells grown de novo in SCM, as while melanocytes share a common precursor with neural cells, melanoma frequently demonstrates divergent behavior in cancer stem cell assays. SCM culture of melanoma cells induced a neural lineage gene expression profile that was not representative of matched patient tissue samples and which could be induced in serum cell lines by switching them into SCM. There was no enrichment for expression of putative melanoma stem cell markers, but the SCM expression profile did overlap significantly with that of SCM cultures of glioma, suggesting that the observed phenotype is media-specific rather than melanoma-specific. Xenografts derived from either culture condition provided the best representation of melanoma in situ. Finally, SCM culture of melanoma did not prevent ongoing acquisition of DNA copy number abnormalities. In conclusion, SCM culture of melanoma does not provide a better representation of the phenotype or genotype of metastatic melanoma, and the resulting neural bias could potentially confound therapeutic target identification.
Gov't Doc #: 22102544
DOI: 10.1002/stem.786
Type: Journal Article
Subjects: Animals
Antigens, Differentiation.genetics.metabolism
Cell Culture Techniques
Cell Line, Tumor.metabolism
Cell Proliferation
Cluster Analysis
Culture Media
DNA Copy Number Variations
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Mice, Inbred NOD
Mice, SCID
Neoplasm Transplantation
Stem Cells.metabolism
Appears in Collections:Journal articles

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