DOI . ORG {
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Detected CMS Systems:
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We began analyzing https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092596, but it redirected us to https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092596. The analysis below is for the second page.
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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.
Title[redir]:
No title found...
Description:
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.
Matching Content Categories {📚}
- Science
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Doi.org utilizes WORDPRESS.
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🌍 Impressive Traffic: 500k - 1M visitors per month
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Keywords {🔍}
cells, melanoma, cell, expression, sox, figure, genes, article, view, google, scholar, cdcd, tumors, shctl, observed, markers, tumor, found, shown, stem, levels, growth, analysis, data, days, positive, cdkd, shrna, neural, immunofluorescence, factor, mitf, cellular, differentiation, phenotype, microscopy, qpcr, crest, cancer, plos, metastasis, heterogeneity, double, properties, analyzed, transfected, gene, scale, human, mel,
Topics {✒️}
cookies plos plos complex fashion [38] sry-box 2 clone a103/m2-7c10/m2-9e3 transforming growth factor-beta contributed reagents/materials/analysis tools open-access article distributed nod/scid mouse strain activin-mediated growth inhibition neural crest-derived melanocytes limb-derived chemotropic semaphorins forkhead-box d3 beadchip humanht-12v4 platform gli2-mediated melanoma invasion gene-set enrichment analysis robust multi-array average patient-derived melanoma metastases slowly-dividing melanoma cells original author tumor-derived cell cultures ncsc-specific gene signature dermis-derived stem cells tcf/lef target genes genome-wide expression profiling human specific cd271-pe metastases-derived xenograft tumors melanoma metastasis gene tumor-initiating cells represents li-cor biosciences depicting active tgfβ-signaling reduced dna-repair capacity stable shrna-mediated knock melanoma tumor-initiating cells pm-derived xenograft tumors dye-retaining mel9-1 cells anti-apoptotic genes ciap1 cell division cycle gene expression profiling sox10-dependent network triggered colony-forming conditions indicating malignant melanoma responsible dye-retaining mel4–7 cells dye-retaining mel4-7 cells gene symbol annotations cd271/cd133 double positive pmc-derived xenograft tumor marker gene expression dye-retaining fraction suggesting cd271-dependent signaling network
Questions {❓}
- Zabierowski SE, Fukunaga-Kalabis M, Li L, Herlyn M (2011) Dermis-derived stem cells: a source of epidermal melanocytes and melanoma?
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