Tie2 Regulates Tumor Metastasis of Oral Squamous Cell Carcinomas

The endothelial-specific receptor, tyrosine kinase with immunoglobulin-like loops and epidermal growth factor homology domains-2 (Tie2) is a member of the tyrosine kinase family and is ubiquitous in normal tissues; however, little is known about the mechanisms and roles of Tie2 in oral squamous cell carcinomas (OSCCs). In the current study, we investigated the expression status of Tie2 in OSCCs by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry and the functional mechanisms of Tie2 using its overexpressed OSCC (oeTie2) cells and Tie2 blocking by its antibody. We found that Tie2 expression was down-regulated significantly (p < 0.05) in OSCCs compared with normal counterparts in vitro and in vivo. Interestingly, oeTie2 cells showed higher cellular adhesion (p < 0.05) and lower cellular invasion (p < 0.05) compared with control cells; whereas there was similar cellular proliferation in both transfectants. Furthermore, cellular adhesion was inhibited and invasion was activated by Tie2 function-blocking antibody (p < 0.05), indicating that Tie2 directly regulates cellular adhesion and invasion. As expected, among the clinical variables analyzed, Tie2-positivity in patients with OSCC was correlated closely with negative lymph node metastasis. These results suggested for the first time that Tie2 plays an important role in tumor metastasis and may be a potential biomarker for OSCC metastasis.