Journal article
Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations
BMC cancer, Vol.16(1), pp.726-726
09/09/2016
DOI: 10.1186/s12885-016-2759-2
PMCID: PMC5017126
PMID: 27613604
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.
Details
- Title: Subtitle
- Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations
- Creators
- Carole Grasso - Malaghan Institute of Medical ResearchMatthew Anaka - Olivia Newton-John Cancer Wellness & Research CentreOliver Hofmann - Harvard UniversityRamakrishna Sompallae - Harvard UniversityKate Broadley - Malaghan Institute of Medical ResearchWinston Hide - Harvard UniversityMichael V. Berridge - Malaghan Institute of Medical ResearchJonathan Cebon - Ludwig Cancer ResearchAndreas Behren - Ludwig Cancer ResearchMelanie J. McConnell - Malaghan Institute of Medical Research
- Resource Type
- Journal article
- Publication Details
- BMC cancer, Vol.16(1), pp.726-726
- Publisher
- BioMed Central
- DOI
- 10.1186/s12885-016-2759-2
- PMID
- 27613604
- PMCID
- PMC5017126
- ISSN
- 1471-2407
- eISSN
- 1471-2407
- Grant note
- ;
- Language
- English
- Date published
- 09/09/2016
- Academic Unit
- Pathology
- Record Identifier
- 9984622049202771
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