Chiappetta Caterina, Leopizzi Martina, Censi Fabiana, Puggioni Chiara, Petrozza Vincenzo, Rocca Carlo D, Di Cristofano Claudio
Department of Medical Surgical Sciences and Biotechnologies, Pathology Unit, ICOT, Sapienza University of Rome, Latina, Italy.
Appl Immunohistochem Mol Morphol. 2014 Mar;22(3):162-70. doi: 10.1097/PDM.0000000000000033.
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.
骨肉瘤是最常见的骨恶性肿瘤。骨肉瘤患者的主要死因是转移潜能增加，而埃兹蛋白的表达与转移发展相关。埃兹蛋白通过将Rho鸟苷酸解离抑制因子（RhoGDI）与Rho鸟苷三磷酸酶（RhoGTPases）分离来与之相互作用，这使得GTPases能够加载GTP，激活RhoA以增加细胞迁移和侵袭。已发现RhoGTPases参与包括癌细胞迁移、侵袭和转移在内的病理过程，并且在许多人类肿瘤（包括Rac1和RhoA）中检测到GTPase本身或Rho信号传导的某些元件的过表达。我们分析了骨肉瘤组织中Rac1和RhoA的表达，以了解埃兹蛋白-Rho家族途径在骨肉瘤转移进展中的作用。此外，我们使用小干扰RNA（siRNA）试验阻断埃兹蛋白的表达，以研究其与骨肉瘤细胞系中RAC1和RHOA表达的可能相关性。我们的免疫组织化学数据显示，许多骨肉瘤的Rac1和RhoA均呈细胞质阳性，并且与埃兹蛋白阴性的病例相比，埃兹蛋白阳性的病例显示出Rac1和RhoA的蛋白表达。埃兹蛋白siRNA转染获得的结果表明，骨肉瘤细胞系中的埃兹蛋白表达可能主要调节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，并且由于埃兹蛋白、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，无转移的骨肉瘤显示出Rac1和RhoA表达阳性，这可能是一个保护因素。
