Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, China.
Histopathology. 2011 Oct;59(4):763-75. doi: 10.1111/j.1365-2559.2011.03993.x.
To investigate whether Oct4, Sox2 and Nanog, three core regulatory factors maintaining pluripotency and self-renewal of embryonic stem cells (ESCs), are coexpressed in human gliomas, and whether their expression might be linked to carcinogenesis and the formation of cancer stem cells (CSCs).
Forty cases of human glioma were examined. The expression of Oct4, Sox2 and Nanog was analysed by immunohistochemistry, reverse transcription polymerase chain reaction and western blot. We found a positive correlation between the expression levels of Oct4, Sox2 and Nanog and tumour malignancy. Immunohistochemistry showed that Oct4 and Nanog were expressed in both the nuclei and the cytoplasm of glioma cells, whereas Sox2 was expressed only in the nuclei. Double immunofluorescence staining revealed that a majority of Oct4-positive cells coexpressed Sox2 and Nanog. More than 50% of Oct4-positive cells coexpressed the putative CSC markers CD133 and Nestin. Moreover, some cells exhibited Oct4 and Nanog immunoexpression in the cytoplasm, but the frequency of positive cells did not correlate with tumour malignancy.
The present findings suggest that ESC-associated pathways are activated in human gliomas and that these may be involved in glioma progression, a role that is distinct from that in ESCs.
研究胚胎干细胞(ESCs)维持多能性和自我更新的三个核心调控因子 Oct4、Sox2 和 Nanog 是否在人神经胶质瘤中共同表达,以及它们的表达是否与致癌作用和癌干细胞(CSC)的形成有关。
我们检测了 40 例人神经胶质瘤。通过免疫组织化学、逆转录聚合酶链反应和 Western blot 分析了 Oct4、Sox2 和 Nanog 的表达。我们发现 Oct4、Sox2 和 Nanog 的表达水平与肿瘤恶性程度呈正相关。免疫组织化学显示 Oct4 和 Nanog 在神经胶质瘤细胞的核和细胞质中均有表达,而 Sox2 仅在核中表达。双重免疫荧光染色显示,大多数 Oct4 阳性细胞共同表达 Sox2 和 Nanog。超过 50%的 Oct4 阳性细胞共同表达 CSC 标记物 CD133 和 Nestin。此外,一些细胞在细胞质中表现出 Oct4 和 Nanog 的免疫表达,但阳性细胞的频率与肿瘤恶性程度无关。
本研究结果提示 ESC 相关途径在人神经胶质瘤中被激活,这些途径可能参与神经胶质瘤的进展,其作用与 ESCs 中的作用不同。