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

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Item Type:Article
Title:The nerve growth factor receptor CD271 is crucial to maintain tumorigenicity and stem-like properties of melanoma cells
Creators Name:Redmer, T. and Welte, Y. and Behrens, D. and Fichtner, I. and Przybilla, D. and Wruck, W. and Yaspo, M.L. and Lehrach, H. and Schaefer, R. and Regenbrecht, C.R.A.
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.
Keywords:Biological Tumor Markers, CD Antigens, Gene Knockdown Techniques, Glycoproteins, Inbred NOD Mice, Melanoma, Meta-Analysis as Topic, Neoplasm Proteins, Neoplastic Stem Cells, Nerve Growth Factor Receptors, Nerve Tissue Proteins, Peptides, SOXE Transcription Factors, Tumor Cell Line, Animals, Mice
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science (U.S.A.)
Volume:9
Number:5
Page Range:e92596
Date:5 May 2014
Additional Information:Erratum in: PLoS ONE 9(8): e105274.
Official Publication:https://doi.org/10.1371/journal.pone.0092596
PubMed:View item in PubMed

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