Correlation of the Rac1/RhoA Pathway With Ezrin Expression in: Gsteosarcoma

摘要

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 Racl and RhoA. We have analyzed Racl 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 immunohistochernical data showed that many osteosarcomas presented cytoplasmatic positivity for both Racl and RhoA and cases, both ezrin positive than ezrin negative, revealed the protein expression of Racl and RhoA. The results obtained by ezrin siRNA transfection showed that ezrin expression in the osteosarcoma cell lines might modulate, mainly, the Racl expression. It is possible that the mechanism of cell motility mediated by Racl and RhoA is maintained in osteosarcomas, and since the expression of ezrin, Racl and RhoA do not correlate with metastatic progression in osteosarcoma. However, osteosarcomas without metastasis displayed a positivity for Racl and RhoA expression compared with metastatic osteosarcomas and this could be a protective factor.