Boeuf S, Kunz P, Hennig T, Lehner B, Hogendoorn Pcw, Bovée Jvmg, Richter W
Division of Experimental Orthopaedics, Orthopaedic University Hospital of Heidelberg, Germany.
J Pathol. 2008 Oct;216(2):158-66. doi: 10.1002/path.2389.
Phenotypic and molecular parallels between the development of chondrosarcoma and the differentiation of chondrocytes in normal growth plate suggest that chondrosarcoma may arise from mesenchymal precursor cells driven towards chondrogenesis. We hypothesized that a comparison between cartilaginous tumours and their possible physiological cells of origin, mesenchymal stem cells (MSCs), might have biological and clinical relevance. MSCs from eight donors were submitted to chondrogenic differentiation in spheroid cultures. Expression profiles of MSCs at days 0, 7, 14, 28 and 42 of chondrogenesis and of 18 chondrosarcomas with different histological grades were studied using a customized cDNA array. Hierarchical clustering of MSC gene expression during chondrogenesis allowed the classification of samples in a pre-chondrogenic and a chondrogenic cluster corresponding to the phenotypes of early and late differentiation stages. The 74 genes differentially expressed between the two clusters were defined as chondrogenesis-relevant genes. Gene expression profiles of chondrosarcoma were submitted to hierarchical clustering on the basis of these chondrogenesis-relevant genes. This analysis allowed clear distinction between grade I and grade III chondrosarcoma and separated grade II chondrosarcoma into two groups. All grade II chondrosarcomas with occurrence of metastasis were found together with the grade III chondrosarcomas in the pre-chondrogenic cluster. This analysis shows that a molecular approach based on the comparison of tumour samples to an in vitro model for chondrogenic differentiation allows a new classification of chondrosarcoma in two clusters. These data suggest that the identification of a pre-chondrogenic and a chondrogenic phenotype for chondrosarcoma by gene expression profiling could develop into a useful tool to predict the clinical behaviour of chondrosarcoma.
软骨肉瘤的发展与正常生长板中软骨细胞的分化之间在表型和分子层面的相似性表明，软骨肉瘤可能起源于被诱导向软骨形成方向发展的间充质前体细胞。我们推测，比较软骨肿瘤与其可能的生理性起源细胞——间充质干细胞（MSC），可能具有生物学和临床意义。来自八位供体的MSC在球体培养中进行软骨分化。使用定制的cDNA阵列研究了软骨分化第0、7、14、28和42天的MSC以及18例不同组织学分级的软骨肉瘤的表达谱。软骨分化过程中MSC基因表达的层次聚类分析将样本分为对应早期和晚期分化阶段表型的软骨形成前簇和软骨形成簇。这两个簇之间差异表达的74个基因被定义为软骨形成相关基因。基于这些软骨形成相关基因，对软骨肉瘤的基因表达谱进行层次聚类分析。该分析能够清晰区分I级和III级软骨肉瘤，并将II级软骨肉瘤分为两组。所有发生转移的II级软骨肉瘤与III级软骨肉瘤一起被归为软骨形成前簇。该分析表明，基于将肿瘤样本与软骨分化体外模型进行比较的分子方法能够对软骨肉瘤进行新的两类聚类。这些数据表明，通过基因表达谱鉴定软骨肉瘤的软骨形成前表型和软骨形成表型可能会成为预测软骨肉瘤临床行为的有用工具。
