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首页> 外文期刊>Glycobiology. >Expression of stage-specific embryonic antigen-4 (SSEA-4) defines spontaneous loss of epithelial phenotype in human solid tumor cells
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Expression of stage-specific embryonic antigen-4 (SSEA-4) defines spontaneous loss of epithelial phenotype in human solid tumor cells

机译：阶段特异性胚胎抗原4（SSEA-4）的表达定义了人实体瘤细胞中上皮表型的自发丧失

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Stage-specific embryonic antigen-4 (SSEA-4) is a glycosphingolipid, which is overexpressed in some cancers and has been linked to disease progression. However, little is known about the functions of SSEA-4 and the characteristics of SSEA-4 expressing tumor cells. Our studies identified SSEA-4 expression on a subpopulation of cells in many solid tumor cell lines but not in leukemic cell lines. Fluorescence-activated cell sorting-sorted SSEA-4(+) prostate cancer cells formed fibroblast-like colonies with limited cell-cell contacts, whereas SSEA-4-cells formed cobblestone-like epithelial colonies. Only colonies derived from SSEA-4(+) cells were enriched for pluripotent embryonic stem cell markers. Moreover, major epithelial cell-associated markers Claudin-7, E-cadherin, ESRP1 and GRHL2 were down-regulated in the SSEA-4(+) fraction of DU145 and HCT-116 cells. Similar to cell lines, SSEA-4(+) primary prostate tumor cells also showed down-regulation of epithelial cell-associated markers. In addition, they showed up-regulation of epithelial-to-mesenchymal transition as well as mesenchymal markers. Furthermore, SSEA-4(+) cells escape from adhesive colonies spontaneously and form invadopodia-like migratory structures, in which SSEA-4, cortactin as well as active pPI3K, pAkt and pSrc are enriched and colocalized. Finally, SSEA-4(+) cells displayed strong tumorigenic ability and stable knockdown of SSEA-4 synthesis resulted in decreased cellular adhesion to different extracellular matrices. In conclusion, we introduce SSEA-4 as a novel marker to identify heterogeneous, invasive subpopulations of tumor cells. Moreover, increased cell-surface SSEA-4 expression is associated with the loss of cell-cell interactions and the gain of a migratory phenotype, suggesting an important role of SSEA-4 in cancer invasion by influencing cellular adhesion to the extracellular matrix.
机译：阶段特异性胚胎抗原4（SSEA-4）是糖鞘脂，在某些癌症中过表达，并与疾病进展相关。然而，关于SSEA-4的功能和表达SSEA-4的肿瘤细胞的特性知之甚少。我们的研究确定了SSEA-4在许多实体肿瘤细胞系中的细胞亚群上的表达，但在白血病细胞系中却没有。荧光激活的细胞分类排序的SSEA-4（+）前列腺癌细胞形成了细胞间接触受限的成纤维细胞样菌落，而SSEA-4细胞则形成了鹅卵石样上皮菌落。仅来自SSEA-4（+）细胞的菌落富集了多能胚胎干细胞标记。此外，DU145和HCT-116细胞的SSEA-4（+）部分中的主要上皮细胞相关标记Claudin-7，E-钙黏着蛋白，ESRP1和GRHL2被下调。与细胞系相似，SSEA-4（+）原发性前列腺肿瘤细胞也显示出上皮细胞相关标记的下调。此外，他们显示上皮到间充质转化以及间充质标记物上调。此外，SSEA-4（+）细胞自发地从黏附集落中逃逸，并形成侵袭伪足样的迁移结构，其中SSEA-4，cortactin以及活性pPI3K，pAkt和pSrc富集并共定位。最后，SSEA-4（+）细胞显示出强大的致瘤能力，SSEA-4合成的稳定敲低导致细胞对不同细胞外基质的粘附减少。总之，我们将SSEA-4作为一种新型标记物来鉴定肿瘤细胞的异质，侵袭性亚群。此外，细胞表面SSEA-4表达的增加与细胞间相互作用的丧失和迁移表型的获得有关，这表明SSEA-4通过影响细胞对细胞外基质的粘附而在癌症侵袭中起着重要作用。

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