Down-regulation of S100A2 in lymph node metastases of head and neck cancer
Down-regulation of S100A2 in lymph node metastases of head and neck cancer
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DOI：
10.1002/hed.20511
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发表时间：
2007-03-01
影响因子：
2.9
通讯作者：
Chen, Zhuo (Georgia)
中科院分区：
文献类型：
--
作者：
Zhang, Xin;Hunt, Jennifer L.;Chen, Zhuo (Georgia)
背景资料。我们的头颈部鳞状细胞癌(SCCHN)基因芯片分析先前证实，S100A2在高转移性686LN-M3S细胞系中下调表达，这是通过使用转移性异种移植鼠模型进行体内选择建立的。S100A2被认为是一种肿瘤抑制因子，与正常组织相比，它在几种类型的原发肿瘤中表达下调。目前仅有少数报道探讨了其在肿瘤转移中的表达状态和功能。为了进一步证实S100A2在人类转移中的下调，我们通过石蜡包埋的SCCHN组织的免疫组织化学分析来检测S100A2的表达。样本包括同一患者的原发SCCHN肿瘤(Tu-1)和受累淋巴结(Met-1)，以及原发灶阴性患者的原发肿瘤(Tu-2)。这些肿瘤大多表达S100A2，但与原发肿瘤相比，淋巴结转移瘤中S100A2的表达呈减少趋势。逆转录-聚合酶链式反应(RT-PCR)和免疫印迹显示S100A2在几个SCCHN细胞系中的表达模式相似。特别是，S100A2在686LN中的表达低于Tu686，在686LN-M3s中几乎检测不到S100A2的表达。对S100A2启动子的进一步研究表明，这些转移衍生物的甲基化强度高于Tu686和686LN。S100A2在SCCHN的淋巴转移中表达下调，提示S100A2可能不是肿瘤抑制因子，而可能在SCCHN的转移中起作用。(C)2006年威利期刊公司。
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. (c) 2006 Wiley Periodicals, Inc.