Expression of ADAMTS4 in Ewing's sarcoma.
Expression of ADAMTS4 in Ewing's sarcoma.
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DOI：
10.3892/ijo_00000706
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发表时间：
2010-09
影响因子：
5.2
通讯作者：
K. Minobe;R. Ono;A. Matsumine;F. Shibata-Minoshima;K. Izawa;T. Oki;J. Kitaura;T. Iino;J. Takita;S. Iwamoto;H. Hori;Y. Komada;A. Uchida;Y. Hayashi;T. Kitamura;T. Nosaka
中科院分区：
文献类型：
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作者：
K. Minobe;R. Ono;A. Matsumine;F. Shibata-Minoshima;K. Izawa;T. Oki;J. Kitaura;T. Iino;J. Takita;S. Iwamoto;H. Hori;Y. Komada;A. Uchida;Y. Hayashi;T. Kitamura;T. Nosaka
尤文氏肉瘤是一种常见于青少年的恶性骨肿瘤。引起EWS的基因突变已被研究，最常见的一种被证明是22号染色体的EWS基因和11号染色体的FLI 1基因之间的融合基因。然而，用于诊断EWS的有用生物标记物的数量有限。在这项研究中，我们确定ADAMTS 4（一个解整合素和金属蛋白酶与血小板反应蛋白基序）作为一个可能的肿瘤标志物EWS使用逆转录病毒介导的信号序列陷阱方法。ADAMTS 4是837个氨基酸的分泌蛋白，预测分子量为98-100 kDa。它是金属蛋白酶家族的成员，主要在软骨和脑中表达，并调节聚集蛋白聚糖的降解。ADAMTS 4被认为与关节炎性疾病和神经胶质瘤有关。在此，我们发现ADAMTS 4 mRNA在所有原发性EWS样品和所有EWS衍生细胞系中表达，而其表达仅在其他实体瘤的小亚群中检测到。ADAMTS 4的表达受EWS-FLI 1融合基因的调控。我们还通过免疫组化证实ADAMTS 4蛋白在EWS患者的肿瘤样品中高度表达。这些结果表明ADAMTS 4是EWS的一种新的肿瘤标志物。
Ewing's sarcoma (EWS) is a malignant bone tumor that frequently occurs in teenagers. Genetic mutations which cause EWS have been investigated, and the most frequent one proved to be a fusion gene between EWS gene of chromosome 22 and the FLI1 gene of chromosome 11. However, a limited numbers of useful biological markers for diagnosis of EWS are available. In this study, we identified ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs) as a possible tumor marker for EWS using the retrovirus-mediated signal sequence trap method. ADAMTS4 is a secreted protein of 837 amino acids with a predicted molecular mass of 98-100 kDa. It is a member of metalloprotease family, is expressed mainly in cartilage and brain, and regulates the degradation of aggrecans. ADAMTS4 has been suggested to be involved in arthritic diseases and gliomas. Herein, we show that ADAMTS4 mRNA was expressed in all primary EWS samples and all EWS-derived cell lines examined, while its expression was detected only in small subpopulations of other solid tumors. Furthermore, ADAMTS4 expression was found to be regulated by EWS-FLI1 fusion gene-dependent manner. We also demonstrated that ADAMTS4 protein was highly expressed in tumor samples of the patients with EWS by using immunohistochemistry. These results suggest that ADAMTS4 is a novel tumor marker for EWS.