Muff Roman, Ram Kumar Ram Mohan, Botter Sander M, Born Walter, Fuchs Bruno
Laboratory for Orthopedic Research, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland.
Sarcoma. 2012;2012:937506. doi: 10.1155/2012/937506. Epub 2012 Nov 13.
Osteosarcoma (OS) is a rare bone neoplasm that affects mainly adolescents. It is associated with poor prognosis in case of metastases formation. The search for metastasis predicting markers is therefore imperative to optimize treatment strategies for patients at risk and important for the search of new drugs for the treatment of this devastating disease. Here, we have analyzed by microarray the differential gene expression in four human and two mouse OS cell line systems consisting of parental cell lines with low metastatic potential and derivatives thereof with increased metastatic potential. Using two osteoblastic cell line systems, the most common OS phenotype, we have identified forty-eight common genes that are differentially expressed in metastatic cell lines compared to parental cells. The identified subset of metastasis relevant genes in osteoblastic OS overlapped only minimally with differentially expressed genes in the other four preosteoblast or nonosteoblastic cell line systems. The results imply an OS phenotype specific expression pattern of metastasis regulating proteins and form a basis for further investigation of gene expression profiles in patients' samples combined with survival analysis with the aim to optimize treatment strategies to develop new drugs and to consequently improve the survival of patients with the most common form of osteoblastic OS.
骨肉瘤(OS)是一种罕见的骨肿瘤,主要影响青少年。如果发生转移,其预后较差。因此,寻找转移预测标志物对于优化高危患者的治疗策略至关重要,对于寻找治疗这种毁灭性疾病的新药也很重要。在这里,我们通过微阵列分析了四个人类和两个小鼠OS细胞系系统中的差异基因表达,这些系统由具有低转移潜能的亲本细胞系及其具有增加转移潜能的衍生物组成。使用两种成骨细胞系系统(最常见的OS表型),我们鉴定出了48个与亲本细胞相比在转移细胞系中差异表达的共同基因。在成骨性OS中鉴定出的与转移相关基因的子集与其他四个前成骨细胞或非成骨细胞系系统中差异表达的基因仅有最小程度的重叠。这些结果暗示了转移调节蛋白的OS表型特异性表达模式,并为进一步研究患者样本中的基因表达谱结合生存分析奠定了基础,目的是优化治疗策略以开发新药,从而提高最常见形式的成骨性OS患者的生存率。