Abstract
We recently reported that low Nm23βH1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23βH1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23βH1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23βH1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Woundβhealing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23βH1 levels following knockdown and overexpression. By immunohistochemistry, Nm23βH1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23βH1 in metastasis suppression. Negative Nm23βH1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23βH1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23βH1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23βH1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens. Β© 2007 WileyβLiss, Inc.