Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Carole Grasso, Matthew Anaka, Oliver Hofmann, Ramakrishna Sompallae, Kate Broadley, Winston Hide, Michael V. Berridge, Jonathan Cebon, Andreas Behren, Melanie J. McConnell

ABSTRACT

BACKGROUND: The heterogeneity and tumourigenicity of metastatic melanoma is attributed to a cancer stem cell model, with CD133 considered to be a cancer stem cell marker in melanoma as well as other tumours, but its role has remained controversial. METHODS: We iteratively sorted CD133+ and CD133- cells from 3 metastatic melanoma cell lines, and observed tumourigenicity and phenotypic characteristics over 7 generations of serial xeno-transplantation in NOD/SCID mice. RESULTS: We demonstrate that iterative sorting is required to make highly pure populations of CD133+ and CD133- cells from metastatic melanoma, and that these two populations have distinct characteristics not related to the cancer stem cell phenotype. In vitro, gene set enrichment analysis indicated CD133+ cells were related to a proliferative phenotype, whereas CD133- cells were of an invasive phenotype. However, in vivo, serial transplantation of CD133+ and CD133- tumours over 7 generations showed that both populations were equally able to initiate and propagate tumours. Despite this, both populations remained phenotypically distinct, with CD133- cells only able to express CD133 in vivo and not in vitro. Loss of CD133 from the surface of a CD133+ cell was observed in vitro and in vivo, however CD133- cells derived from CD133+ retained the CD133+ phenotype, even in the presence of signals from the tumour microenvironment. CONCLUSION: We show for the first time the necessity of iterative sorting to isolate pure marker-positive and marker-negative populations for comparative studies, and present evidence that despite CD133+ and CD133- cells being equally tumourigenic, they display distinct phenotypic differences, suggesting CD133 may define a distinct lineage in melanoma. More... »

PAGES

726

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12885-016-2759-2

DOI

http://dx.doi.org/10.1186/s12885-016-2759-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1001777911

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27613604


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