title: Melanoblasts in culture as an in vitro system to determine molecular changes in melanoma.
abstract: 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.
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Anja Katrin
authors.initials: AK
authors.lastname: Bosserhoff
authors.forename: Lisa
authors.initials: L
authors.lastname: Ellmann
authors.forename: Silke
authors.initials: S
authors.lastname: Kuphal
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D051929:CD146 Antigen / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D054337:Cell Dedifferentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D019334:Endothelin-3 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D016023:Integrins / Q000235:genetics; D008297:Male; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D050809:POU Domain Factors / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D055757:SOXE Transcription Factors / Q000235:genetics; D000071250:Snail Family Transcription Factors; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D051929:CD146 Antigen; D015820:Cadherins; D019334:Endothelin-3; C111572:GPR37L1 protein, human; C099972:H-cadherin; C497442:HIF1A protein, human; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016023:Integrins; C497902:MCAM protein, human; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D050809:POU Domain Factors; D051761:Paired Box Transcription Factors; D043562:Receptors, G-Protein-Coupled; C000604407:SNAI1 protein, human; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D000071250:Snail Family Transcription Factors; D020825:T-Box Domain Proteins; C106884:TBX3 protein, human; D014157:Transcription Factors; D051176:beta Catenin; C085076:transcription factor Brn-2; D016222:Fibroblast Growth Factor 2; D020794:Receptor Protein-Tyrosine Kinases