Anterior gradient 2: A novel sensitive tumor marker for metastatic oral cancer

• A highly metastatic subpopulation, HSC-3-5, is isolated and well characterized.
• According to microarray analysis, AGR2 is identified to be a potential tumor marker.
• AGR2 is involved in the regulation of cell migration.
• AGR2 is confirmed as a sensitive tumor marker for metastatic oral cancer.

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.