Melanoblasts in culture as an in vitro system to determine molecular changes in melanoma
| Autor: | Anja Katrin, Bosserhoff, Lisa, Ellmann, Silke, Kuphal |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Integrins Gene Expression Bone Morphogenetic Protein 4 CD146 Antigen Receptors G-Protein-Coupled Cell Movement Cell Line Tumor Cell Adhesion Humans Paired Box Transcription Factors Melanoma PAX3 Transcription Factor Cells Cultured beta Catenin Cell Proliferation Homeodomain Proteins Endothelin-3 SOXE Transcription Factors Stem Cells Receptor Protein-Tyrosine Kinases Cell Dedifferentiation Cadherins Hypoxia-Inducible Factor 1 alpha Subunit POU Domain Factors Melanocytes Fibroblast Growth Factor 2 Snail Family Transcription Factors T-Box Domain Proteins Transcription Factors |
| Zdroj: | Experimental dermatology. 20(5) |
| ISSN: | 1600-0625 |
| Popis: | Many consolidated findings have revealed that cancer formation resembles events of embryonic development. In particular, the network of transcription factors and adhesion molecules is very similar when comparing neural crest-derived melanoblasts and melanoma cells. The main difference is found in the manifestation of distinct genes in melanoma, whereas in neural crest cells gene expression is tightly regulated to promote either a migratory or stationary phenotype. We established a cell culture system to generate melanoblast-related cells (MBrc) out of melanocytes as originally described by Cook et al. First, we confirmed the typical gene expression pattern of BRN-2, SOX10, PAX3 and EDNRB. Furthermore, we identified enhanced migration and proliferation similar to that of melanoma cells. Our intention of using this system was to classify the known 'melanoma-associated genes' into a subgroup of genes solely regulated by the differentiation process and a second subgroup that is unaffected by differentiation and is potentially important to the stabilization of a melanoma phenotype. The expression of melanoma-associated genes (N-cadherin, MUC-18, integrin β3, α3, α5, αv, SLUG, TBX3, HIF1-α, BMP-4 and bFGF) was enhanced in MBrc which were de-differentiated out of melanocytes. E-cadherin, H-cadherin and β-catenin, prevalently found to be downregulated in melanoma, were diminished in MBrc. Remarkably, the transcription factor SNAIL was unaffected by differentiation and could be one key molecule in early melanoma development that is of prevailing importance. In summary, we feel that the analysis of MBrc generated in a reproducible system will give new insight into the role and importance of melanoma-associated genes. |
| Databáze: | OpenAIRE |
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