Down-regulation of S100A2 in lymph node metastases of head and neck cancer.

Abstract

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. 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). 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. 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.