Abstract
In 2012, oral cancer is the 5th leading cause of death in cancer and the mortality rate of oral cancer has dramatically increased 20.7% in the past 10 years in Taiwan. Cancer metastasis is a common cause of failure in cancer therapy. However, over 60% of oral cancer patients present with advanced stage disease, and the five-year survival rates of these patients decrease from 72.6% to 20% as the stage become more advanced. In order to manage oral cancer, identification of metastasis biomarker and mechanism is critical. In this study, we use a pair of oral squamous cell carcinoma lines, OC3, and invasive OC3-I5 as a model system to examine invasive mechanism and to identify potential therapeutic targets. We use two-dimensional differential gel electrophoresis (2D-DIGE) and matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI-TOF/TOF MS) to examine the global protein expression changes between OC3 and invasive OC3-I5. A proteomic study reveal that invasive properties alter the expression of 104 cytosolic proteins and 151 secreted proteins in OC3-I5 cells comparing to OC3 cells. Many potential proteins have been validated by immunoblotting. Further studies have used RNA interference technique to monitor the influence of progesterone receptor membrane component 1 (PGRMC1) and cytochrome P450 2J2 (CYP2J2) proteins in invasion and evaluate their potency in regulating invasion and the mechanism they involved. Moreover, in mouse model, PGRMC1 is shown to influence not only migration and invasion but also metastasis in vivo. Taken together, the proteomic approach allows us to identify numerous proteins, including PGRMC1 and CYP2J2, involved in invasion mechanism. Our results provide useful diagnostic markers and therapeutic candidates for the treatment of oral cancer invasion.