ORIGINAL ARTICLE DOWN-REGULATION OF S100A2 IN LYMPH NODE METASTASES OF HEAD AND NECK CANCER

Abstract: Background. Our cDNA microarray analysis of squamous cell carcinoma of the head and neck (SCCHN) previ-ously identified that S100A2 was down-regulated in highly meta-static 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 sev-eral types of primary tumor as compared with the normal tissue. Only a few reports have explored its expression status and func-tion in metastasis. Methods. To further confirm down-regulation of S100A2 in human metastasis, we examined S100A2 expression using im-munohistochemical analysis of paraffin-embedded SCCHN tis-sues. The samples included primary SCCHN tumors (Tu-1) and involved lymph nodes (Met-1) from the same patients, and pri-mary 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 pat-tern 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 de-rivatives 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 puta-tive tumor suppressor, S100A2 may play a role in the metastasi