Background: Our cDNA microarray analysis of squamous cell carcinoma of the head and neck (SCCHN) previously identified that S100A2 was down-regulated in highly metastatic 686LN-M3s cell lines established through in vivo selection using a metastatic xenograft mouse model. S100A2, a putative tumor suppressor, has been found to be down-regulated in several types of primary tumor as compared with the normal tissue. Only a few reports have explored its expression status and function in metastasis.
Methods: To further confirm down-regulation of S100A2 in human metastasis, we examined S100A2 expression using immunohistochemical analysis of paraffin-embedded SCCHN tissues. The samples included primary SCCHN tumors (Tu-1) and involved lymph nodes (Met-1) from the same patients, and primary tumors in node-negative patients (Tu-2).
Results: Most of these tumors expressed S100A2 but lymph node metastases showed a pattern of reduced staining for S100A2 compared with primary tumors. A similar expression pattern of S100A2 was also observed in several SCCHN cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting. Particularly, S100A2 expression was lower in 686LN than Tu686 and hardly detectable in the metastatic derivatives 686LN-M3s. Further study of S100A2 promoter showed higher methylation intensity in these metastatic derivatives than in Tu686 and 686LN.
Conclusions: S100A2 was down-regulated in lymph node metastasis of SCCHN, suggesting that instead of being a putative tumor suppressor, S100A2 may play a role in the metastasis of SCCHN.