Bertucci François, Pages Cécile, Finetti Pascal, Rochaix Philippe, Lamant Laurence, Devilard Elizabeth, Nguyen Cathy, Houlgatte Rémi, Birnbaum Daniel, Xerri Luc, Brousset Pierre
Departments of Medical Oncology, UMR599 INSERM, Institut Paoli Calmettes, Marseille, France.
Anticancer Res. 2007 Sep-Oct;27(5A):3441-9.
Identification of markers associated with melanoma progression is crucial to identify new prognostic and/or therapeutic targets.
By using DNA microarrays, two human melanoma cell lines, M4Be and Tw12, derived from the same tumor, but with different metastatic potential, were profiled. Western blot of cell lines, immunohistochemistry on melanoma biopsies and in silico analyses validated and extended our results.
Thirty-six clones were differentially-expressed between the two cell lines, representing 33 named genes and 2 expressed sequence tags. The most up-regulated gene in the strongly metastatic clone Tw12 was CD10. Protein analysis with anti-CD1O antibody confirmed this finding in cell lines and clinical samples with expression being more frequent in metastatic compared to primary tumors. Many up-regulated genes were involved in angiogenesis, invasion, growth and apoptosis. Down-regulated genes included tumor suppressor genes and those were involved in differentiation.
We identified several genes the expression of which is associated with metastatic progression in human melanoma cells. Although further analyses are warranted to clarify their exact role in tumor progression, they might lead to new prognostic markers and/or molecular therapeutic targets in metastatic melanoma.
鉴定与黑色素瘤进展相关的标志物对于确定新的预后和/或治疗靶点至关重要。
利用DNA微阵列技术，对源自同一肿瘤但具有不同转移潜能的两个人黑色素瘤细胞系M4Be和Tw12进行了基因表达谱分析。通过细胞系的蛋白质印迹分析、黑色素瘤活检组织的免疫组织化学分析以及计算机分析对结果进行了验证和扩展。
两个细胞系之间有36个克隆存在差异表达，代表33个已命名基因和2个表达序列标签。在高转移克隆Tw12中上调最明显的基因是CD10。用抗CD10抗体进行的蛋白质分析在细胞系和临床样本中证实了这一发现，与原发性肿瘤相比，转移性肿瘤中该蛋白的表达更为常见。许多上调基因参与血管生成、侵袭、生长和凋亡过程。下调基因包括肿瘤抑制基因以及那些参与分化的基因。
我们鉴定出了几个基因，其表达与人黑色素瘤细胞的转移进展相关。尽管需要进一步分析以阐明它们在肿瘤进展中的确切作用，但它们可能会成为转移性黑色素瘤新的预后标志物和/或分子治疗靶点。
