Down-regulation of plakoglobin in soft tissue sarcoma is associated with a higher risk of pulmonary metastasis.
Down-regulation of plakoglobin in soft tissue sarcoma is associated with a higher risk of pulmonary metastasis.
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发表时间：
2008-03
影响因子：
2
通讯作者：
Y. Kanazawa;Y. Ueda;Miyako Shimasaki;S. Katsuda;N. Yamamoto;K. Tomita;H. Tsuchiya
中科院分区：
文献类型：
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作者：
Y. Kanazawa;Y. Ueda;Miyako Shimasaki;S. Katsuda;N. Yamamoto;K. Tomita;H. Tsuchiya
软组织肉瘤（STS）表现出侵袭性和转移潜力，这取决于它们的位置。关于其生物侵袭性的确切分子机制的信息很少。为了确定与STS差异相关的基因，我们比较了STS正位和异位移植模型的基因表达谱，并验证了其在人类STS中的意义。将人纤维肉瘤HT1080细胞分别植入裸鼠股四头肌或脚垫，通过cDNA阵列比较肿瘤的基因表达谱。采用实时RT-PCR和免疫组织化学方法检测鉴定基因在模型肿瘤及临床STS中的mRNA和蛋白水平。移植的HT1080细胞在不同的移植位置表现出不同的生长和转移潜能。cDNA阵列分析显示肌内植入组血小板红蛋白基因表达降低，real-time RT-PCR证实有统计学意义（p = 0.04）。在植入足垫的肿瘤细胞中，血小板红蛋白在细胞质中有弥漫性免疫定位，而在肌肉中没有。临床STS实时RT-PCR检测结果显示，肺转移的原发性肉瘤组织中血小板红蛋白/甘油醛3-磷酸脱氢酶（G3PDH）比值（0.92）显著低于无转移的原发性肉瘤组织（6.58）（p < 0.0001），血小板红蛋白基因高表达的STS患者预后良好。提示血小板红蛋白基因表达水平可作为人类STS转移和预后的新的生物标志物。
Soft tissue sarcomas (STS) behave with aggressiveness and metastatic potential, that can vary depending on their locations. There has been little information on the exact molecular mechanisms involved in their biological aggressiveness. To identify genes involved in the differences, the gene expression profiles were compared between STS-orthotopic and heterotopic implanted models, and their significance in human STS was verified. Human fibrosarcoma HT1080 cells were implanted either in the quadriceps femoris muscles or footpads of nude mice, and the gene expression profiles of the tumors were compared by cDNA arrays. The mRNA and protein levels of the identified genes were examined by both real time RT-PCR and immunohistochemistry not only in the tumors of the models, but also in clinical STS. The implanted HT1080 cells demonstrated different growth and metastatic potentials depending on their implant locations. cDNA array analyses showed decreased expression of the plakoglobin gene in the intramuscle-implanted group, which was statistically confirmed by real-time RT-PCR (p = 0.04). Plakoglobin was immunolocalized diffusely in the cytoplasm of tumor cells implanted in the footpads, but not those in the muscle. Real-time RT-PCR assays of clinical STS showed that the mean plakoglobin/glyceraldehyde 3-phosphate dehydrogenase (G3PDH) ratio in primary sarcoma tissues with pulmonary metastases (0.92) was significantly lower than in those without metastasis (6.58) (p < 0.0001), and that STS cases with high plakoglobin gene expression had an excellent prognosis. These results suggest that plakoglobin gene expression level might be useful as a new biomarker for metastasis and prognosis of human STS.