Melanoblasts in culture as an in vitro system to determine molecular changes in melanoma
Melanoblasts in culture as an in vitro system to determine molecular changes in melanoma
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DOI：
10.1111/j.1600-0625.2011.01271.x
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发表时间：
2011-05-01
影响因子：
3.6
通讯作者：
Kuphal, Silke
中科院分区：
文献类型：
--
作者：
Bosserhoff, Anja Katrin;Ellmann, Lisa;Kuphal, Silke
许多巩固的发现表明，癌症的形成类似于胚胎发育过程。特别是，当比较神经嵴来源的黑素母细胞和黑色素瘤细胞时，转录因子和黏附分子的网络非常相似。主要的区别是在黑色素瘤中发现了不同的基因表现，而在神经脊细胞中，基因表达受到严格的调控，以促进迁徙或静止的表型。我们建立了一个细胞培养系统来从黑素细胞中产生黑素母细胞相关细胞(MBRC)，这最初是由Cook等人描述的。首先，我们确定了BRN-2、Sox10、PAX3和EDNRB的典型基因表达模式。此外，我们还发现了类似于黑色素瘤细胞的迁移和增殖增强。我们使用这一系统的目的是将已知的黑色素瘤相关基因分类为仅受分化过程调节的基因亚组和不受分化影响的第二亚组，这对黑色素瘤表型的稳定具有潜在的重要意义。黑色素瘤相关基因(N-钙粘蛋白、MUC-18、整合素β3、α3、α5、αv、slug、Tbx3、HIF1-α、BMP-4和bFGF)在去分化的MBRC中表达增强。在黑色素瘤中普遍下调的E-钙粘蛋白、H-钙粘蛋白和β-连环素在MBRC中表达减少。值得注意的是，转录因子Snail不受分化的影响，可能是早期黑色素瘤发展的关键分子，具有普遍重要性。综上所述，我们认为，在可重复的系统中产生的MBRC的分析将为黑色素瘤相关基因的作用和重要性提供新的见解。
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 beta 3, alpha 3, alpha 5, alpha v, SLUG, TBX3, HIF1-alpha, BMP-4 and bFGF) was enhanced in MBrc which were de-differentiated out of melanocytes. E-cadherin, H-cadherin and beta-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.