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

AbstractBACKGROUND:
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.
AuthorsTorben Redmer, Yvonne Welte, Diana Behrens, Iduna Fichtner, Dorothea Przybilla, Wasco Wruck, Marie-Laure Yaspo, Hans Lehrach, Reinhold Schäfer, Christian R A Regenbrecht
JournalPloS one (PLoS One) Vol. 9 Issue 5 Pg. e92596 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID24799129 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • AC133 Antigen
  • Antigens, CD
  • Biomarkers, Tumor
  • Glycoproteins
  • NGFR protein, human
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • Receptors, Nerve Growth Factor
  • SOX10 protein, human
  • SOXE Transcription Factors
Topics
  • AC133 Antigen
  • Animals
  • Antigens, CD (biosynthesis, genetics)
  • Biomarkers, Tumor (biosynthesis, genetics)
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • Glycoproteins (biosynthesis, genetics)
  • Humans
  • Male
  • Melanoma (genetics, metabolism, pathology)
  • Meta-Analysis as Topic
  • Mice
  • Mice, Inbred NOD
  • Neoplasm Proteins (biosynthesis, genetics)
  • Neoplastic Stem Cells (metabolism, pathology)
  • Nerve Tissue Proteins (biosynthesis, genetics)
  • Peptides (genetics)
  • Receptors, Nerve Growth Factor (biosynthesis, genetics)
  • SOXE Transcription Factors (biosynthesis, genetics)

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