The prevention of oral squamous cell carcinoma metastasis to improve overall patient survival has provided the rationale for biomarker development. We used the Transwell invasion assay to isolate a highly metastatic subpopulation, HSC-3-5 cells, with almost the same genetic background as HSC-3 cells but a higher metastatic capacity accompanied by cytoskeletal rearrangements and mesenchymal transformation. HSC-3-5 cells also showed tumorigenic and metastatic characteristics in vivo. In addition, Anterior gradient 2 ( agr2), a pro-oncogenic signaling intermediate, was identified from gene expression profiling, and overexpression of AGR2 showed a positive correlation with oral tumor metastasis. Taken together, our data suggest that AGR2 may be a novel sensitive biomarker for metastatic oral cancer.
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