Background: The main reasons of poor prognosis of oral cavity cancer are most lesions diagnosed in advanced stage, secondary cancer occurrence, local recurrence, and/or metastasis. Currently, the key molecules for oral squamous cell carcinoma to associate with cancer progression and as specific markers to support treatment in clinic remain unavailable.
Methodologies: Isobaric-tagging and SILAC-assisted quantitative proteomics were implemented to determine the dys-regulated protein and phosphoprotein candidates in conditional media and membrane parts of oral cancer cell lines with high and low metastatic ability.
Findings: Eighty five dys-regulated secretory protein candidates were discovered from the 3616 proteins identified in conditional media of the cultured oral cancer cells with various metastatic abilities. Using the enriched membrane compartments, 52 dys-regulated protein candidates were found from the 4111 quantified proteins. Three secretory protein candidates were further confirmed to increase in the metastatic cancer cell lines by Western blot. One of membrane protein candidate, claudin-1, was confirmed to be overexpressed in oral cancer cell lines with nodal metastatic ability in mouse model.
Concluding: Using the established oral cancer cell lines with high and low metastatic ability to explore the protein candidates and signaling drive the malignancy of oral cancer cells. Eighty five dys-regulated secretory proteins and 52 dys-regulated protein candidates in membrane parts were discovered. The overexpression of claudin-1 in oral squamous cell carcinoma has been reported by several research teams, which support the confidence of our finding. Currently, the abundance of the discovered secretory and membrane candidates in tissues and bio-fluid samples from oral cancer patients are under evaluated by immunohistochemical staining, ELISA and MRM MS assays. The roles of those candidates in tumor development will be examined in animal models to find out the molecules play a key role in metastasis of oral cavity cancers.