| Summary: | 博士 === 長庚大學 === 生物醫學研究所 === 97 === Oral squamous cell carcinoma (OSCC) is the 11th most common cancer worldwide, and is associated with a high death rate. Its high death rate is mainly due to the OSCC being usually diagnosed in advanced stages. Oral cancer is a complex disease arising in various organs, including tongue, buccal, oropharynx, gum, soft palate, hard palate, lips, tonsil and the floor of the mouth. More than 90% of oral cancer cases are oral squamous cell carcinomas (OSCC), which are associated with a very poor prognosis. Approximately 50–70% of OSCC patients die within 5 years of diagnosis, mainly due to local and neck recurrence, metastasis to the esophagus or lungs, and/or the development of additional primary cancers. At present, there are no suitable markers for detecting and/or monitoring OSCC in body fluids/tissues. Therefore, biomarkers for early detection and targets for therapy of oral cancer are urgently needed. Here, we used 1D SDS-PAGE and MALDI-TOF MS to systematically analyze the secretomes of two OSCC cell lines (OEC-M1 and SCC4). Thirty-seven proteins were detected in the conditioned media from the two cell lines (27 proteins in SCC4 and 27 proteins in OEC-M1), and 17 proteins were identified in both cell lines. Some of these proteins have been previously considered as potential serum tumor markers, but most of them have not been reported previously to be secreted by oral cancer cell lines. We confirmed 15 of these proteins by western blot, including Mac-2 binding protein (Mac-2 BP) and fascin. Immunohistochemical analysis revealed that >60% of oral cancer biopsies examined (146 cases for Mac-2 BP and 152 cases for fascin) show overexpression of Mac-2 BP or fascin as compared to the non-tumor counter parts. We have also developed ELISA for Mac-2BP and fascin and measured their serum levels in healthy controls and oral cancer patients. The serum levels of Mac-2 BP were significantly higher in OSCC patients (n = 106) versus those in healthy controls (n = 91) (8.06 ± 5.76 vs. 5.54 ± 5.1 g/ml; p < 0.0001). Finally, RNA interference-based knock-down of Mac-2 BP and fascin expression in OSCC cells revealed for the first time that these two proteins are involved in regulating growth and motility of OSCC cells. Collectively, our data shows that analysis of cancer cell-secreted proteomes is a feasible strategy for searching biomarkers of oral cancer. Mac-2 BP and fascin represent two such proteins, and both proteins participate in the regulation of cell growth and mobility.
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