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PLoS One. 2014 May 5;9(5):e92596. doi: 10.1371/journal.pone.0092596. eCollection 2014.

The nerve growth factor receptor CD271 is crucial to maintain tumorigenicity and stem-like properties of melanoma cells.

Author information

1
Institute for Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
2
Institute of Pathology - University Hospital Berlin, Berlin, Germany.
3
Experimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin, Germany.
4
Institute of Pathology - University Hospital Berlin, Berlin, Germany; Comprehensive Cancer Center Charité - University Hospital Berlin, Berlin, Germany.
5
Institute of Pathology - University Hospital Berlin, Berlin, Germany; Laboratory of Functional Genomics (LFGC) - University Hospital Berlin, Berlin, Germany.
6
Max-Planck Institute for Molecular Genetics, Berlin, Germany.
7
Institute of Pathology - University Hospital Berlin, Berlin, Germany; Laboratory of Functional Genomics (LFGC) - University Hospital Berlin, Berlin, Germany; Comprehensive Cancer Center Charité - University Hospital Berlin, Berlin, Germany.

Erratum in

  • PLoS One. 2014;9(8):e105274.

Abstract

BACKGROUND:

Large-scale genomic analyses of patient cohorts have revealed extensive heterogeneity between individual tumors, contributing to treatment failure and drug resistance. In malignant melanoma, heterogeneity is thought to arise as a consequence of the differentiation of melanoma-initiating cells that are defined by cell-surface markers like CD271 or CD133.

RESULTS:

Here we confirmed that the nerve growth factor receptor (CD271) is a crucial determinant of tumorigenicity, stem-like properties, heterogeneity and plasticity in melanoma cells. Stable shRNA mediated knock-down of CD271 in patient-derived melanoma cells abrogated their tumor-initiating and colony-forming capacity. A genome-wide expression profiling and gene-set enrichment analysis revealed novel connections of CD271 with melanoma-associated genes like CD133 and points to a neural crest stem cell (NCSC) signature lost upon CD271 knock-down. In a meta-analysis we have determined a shared set of 271 differentially regulated genes, linking CD271 to SOX10, a marker that specifies the neural crest. To dissect the connection of CD271 and CD133 we have analyzed 10 patient-derived melanoma-cell strains for cell-surface expression of both markers compared to established cell lines MeWo and A375. We found CD271+ cells in the majority of cell strains analyzed as well as in a set of 16 different patient-derived melanoma metastases. Strikingly, only 2/12 cell strains harbored a CD133+ sub-set that in addition comprised a fraction of cells of a CD271+/CD133+ phenotype. Those cells were found in the label-retaining fraction and in vitro deduced from CD271+ but not CD271 knock-down cells.

CONCLUSIONS:

Our present study provides a deeper insight into the regulation of melanoma cell properties and points CD271 out as a regulator of several melanoma-associated genes. Further, our data strongly suggest that CD271 is a crucial determinant of stem-like properties of melanoma cells like colony-formation and tumorigenicity.

PMID:
24799129
PMCID:
PMC4010406
DOI:
10.1371/journal.pone.0092596
[Indexed for MEDLINE]
Free PMC Article

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