SOX2 and nestin expression in human melanoma: an immunohistochemical and experimental study.
SOX2 and nestin expression in human melanoma: an immunohistochemical and experimental study.
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DOI：
10.1111/j.1600-0625.2011.01247.x
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发表时间：
2011-04
影响因子：
3.6
通讯作者：
Murphy GF
中科院分区：
文献类型：
--
作者：
Laga AC;Zhan Q;Weishaupt C;Ma J;Frank MH;Murphy GF
SOX2是一种胚胎神经嵴干细胞转录因子，最近被证明在人类黑色素瘤中表达，并与实验性肿瘤生长相关。SOX2与编码巢蛋白的基因增强子区结合，巢蛋白也是一种神经祖细胞生物标志物。为了进一步确定SOX2和巢蛋白之间的潜在关系，我们检测了135个黑色素瘤和37个黑素细胞痣的共表达模式。27例黑色素瘤组织切片的免疫组化染色显示SOX2阳性、梭形细胞形状和外周巢蛋白分布模式之间存在关联。相反，sox2阴性细胞主要呈上皮样，并表现出巢蛋白的细胞质模式。在组织微阵列中，共表达与肿瘤进展相关，只有11%的痣共表达SOX2和nestin，而转移性黑色素瘤的这一比例为65%，并且初步与临床结果相关。差异表达组成型SOX2的人类黑色素瘤细胞系显示SOX2与巢蛋白表达呈正相关。这些细胞系在小鼠皮下和人皮移植真皮中生长的实验性黑素瘤维持了sox2阳性、梭形细胞形状和外周巢蛋白分布之间的关联。此外，在sox2敲除的A2058黑色素瘤细胞产生的异种移植物中观察到巢蛋白分布的细胞质模式，与转染非靶shRNA的A2058对照细胞生长的肿瘤中观察到的周围巢蛋白分布模式形成对比。总的来说，这些数据进一步支持SOX2与人类黑色素瘤中巢蛋白表达之间的生物学意义上的联系。
SOX2 is an embryonic neural crest stem-cell transcription factor recently shown to be expressed in human melanoma and to correlate with experimental tumor growth. SOX2 binds to an enhancer region of the gene that encodes for nestin, also a neural progenitor cell biomarker. To define further the potential relationship between SOX2 and nestin, we examined co-expression patterns in 135 melanomas and 37 melanocytic nevi. Immunohistochemical staining in 27 melanoma tissue sections showed an association between SOX2 positivity, spindle cell shape and a peripheral nestin distribution pattern. In contrast, SOX2-negative cells were predominantly epithelioid, and exhibited a cytoplasmic pattern for nestin. In tissue microarrays, co-expression correlated with tumor progression, with only 11% of nevi co-expressing SOX2 and nestin in contrast to 65% of metastatic melanomas, and preliminarily, with clinical outcome. Human melanoma lines that differentially expressed constitutive SOX2 revealed a positive correlation between SOX2 and nestin expression. Experimental melanomas grown from these respective cell lines in murine subcutis and dermis of xenografted human skin maintained the association between SOX2-positivity, spindle cell shape, and peripheral nestin distribution. Moreover, the cytoplasmic pattern of nestin distribution was observed in xenografts generated from SOX2-knockdown A2058 melanoma cells, in contrast to the periperhal nestin pattern seen in tumors grown from A2058 control cells transfected with non-target shRNA. In aggregate, these data further support a biologically significant linkage between SOX2 and nestin expression in human melanoma.
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影响因子：
3.6
作者：
Bakos, Renato M.;Maier, Tanja;Berking, Carola
通讯作者：
Berking, Carola
影响因子：
11.2
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Alonso, Soledad R.;Tracey, Lorraine;Rodriguez-Peralto, Jose L.
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