Correlation of the Rac1/RhoA Pathway With Ezrin Expression in Osteosarcoma
Correlation of the Rac1/RhoA Pathway With Ezrin Expression in Osteosarcoma
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DOI：
10.1097/pdm.0000000000000033
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发表时间：
2014-03-01
影响因子：
1.6
通讯作者：
Di Cristofano, Claudio
中科院分区：
文献类型：
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作者：
Chiappetta, Caterina;Leopizzi, Martina;Di Cristofano, Claudio
骨肉瘤是最常见的骨恶性肿瘤。骨肉瘤死亡的主要原因是转移潜力的增加，并且ezrin表达与转移发展相关。 Ezrin 通过将 RhoGDI 与 RhoGTPases 解离来与 RhoGDI 相互作用，从而使 GTPases 能够装载 GTP，激活 RhoA 以增加细胞迁移和侵袭。人们发现 RhoGTP 酶有助于病理过程，包括癌细胞迁移、侵袭和转移，以及 GTP 酶本身或在许多人类肿瘤（包括 Rac1 和 RhoA）中检测到的一些 Rho 信号元件的过度表达。我们分析了骨肉瘤组织中 Rac1 和 RhoA 的表达，以了解 ezrin-Rho 家族通路在骨肉瘤转移进展中的作用。此外，我们使用 siRNA 测定阻断了 ezrin 表达，以研究与骨肉瘤细胞系中 RAC1 和 RHOA 表达的可能相关性。我们的免疫组织化学数据显示，许多骨肉瘤呈现 Rac1 和 RhoA 的细胞质阳性，并且 ezrin 阳性的病例比 ezrin 阴性的病例显示 Rac1 和 RhoA 的蛋白表达。 ezrin siRNA转染的结果表明，骨肉瘤细胞系中ezrin的表达可能主要调节Rac1的表达。 Rac1 和 RhoA 介导的细胞运动机制可能在骨肉瘤中得以维持，并且由于 ezrin、Rac1 和 RhoA 的表达与骨肉瘤的转移进展无关。然而，与转移性骨肉瘤相比，未发生转移的骨肉瘤表现出 Rac1 和 RhoA 表达阳性，这可能是一种保护因素。
Osteosarcoma is the most common malignant tumor of the bone. The major cause of death in osteosarcoma is the increase in metastatic potential, and the ezrin expression has been correlated with the metastasis development. Ezrin interacts with RhoGDI by dissociating it from RhoGTPases, which allow GTPases to load with GTP, activate RhoA to increase cell migration, and invasion. RhoGTPases have been found to contribute to pathologic processes including cancer cell migration, invasion, and metastasis and overexpression of either the GTPase itself or some elements of Rho signaling that have been detected in many human tumors, including Rac1 and RhoA. We have analyzed Rac1 and RhoA expression in the osteosarcoma tissues to understand the role of the ezrin-Rho family pathway in osteosarcoma metastatic progression. Moreover, we have blocked the ezrin expression using siRNA assay to investigate a possible correlation with RAC1 and RHOA expression in the osteosarcoma cell lines. Our immunohistochemical data showed that many osteosarcomas presented cytoplasmatic positivity for both Rac1 and RhoA and cases, both ezrin positive than ezrin negative, revealed the protein expression of Rac1 and RhoA. The results obtained by ezrin siRNA transfection showed that ezrin expression in the osteosarcoma cell lines might modulate, mainly, the Rac1 expression. It is possible that the mechanism of cell motility mediated by Rac1 and RhoA is maintained in osteosarcomas, and since the expression of ezrin, Rac1 and RhoA do not correlate with metastatic progression in osteosarcoma. However, osteosarcomas without metastasis displayed a positivity for Rac1 and RhoA expression compared with metastatic osteosarcomas and this could be a protective factor.