Zhang Quan Bin, Ji Xiao Yan, Huang Qiang, Dong Jun, Zhu Yu De, Lan Qing
Neurosurgical Department and Brain Tumor Research Laboratory, Second Affiliated Hospital of Suzhou University, Suzhou 215004, China.
Cell Res. 2006 Dec;16(12):909-15. doi: 10.1038/sj.cr.7310104.
Understanding of the differentiation profile of brain tumor stem cells (BTSCs), the key ones among tumor cell population, through comparison with neural stem cells (NSCs) would lend insight into the origin of glioma and ultimately yield new approaches to fight this intractable disease. Here, we cultured and purified BTSCs from surgical glioma specimens and NSCs from human fetal brain tissue, and further analyzed their cellular biological behaviors, especially their differentiation property. As expected, NSCs differentiated into mature neural phenotypes. In the same differentiation condition, however, BTSCs exhibited distinguished differences. Morphologically, cells grew flattened and attached for the first week, but gradually aggregated and reformed floating tumor sphere thereafter. During the corresponding period, the expression rate of undifferentiated cell marker CD133 and nestin in BTSCs kept decreasing, but 1 week later, they regained ascending tendency. Interestingly, the differentiated cell markers GFAP and beta-tubulinIII showed an expression change inverse to that of undifferentiated cell markers. Taken together, BTSCs were revealed to possess a capacity to resist differentiation, which actually represents the malignant behaviors of glioma.
通过与神经干细胞(NSCs)比较来了解脑肿瘤干细胞(BTSCs,肿瘤细胞群体中的关键细胞)的分化特征,将有助于深入了解胶质瘤的起源,并最终产生对抗这种难治性疾病的新方法。在此,我们从手术切除的胶质瘤标本中培养并纯化了BTSCs,从人胎儿脑组织中培养并纯化了NSCs,并进一步分析了它们的细胞生物学行为,尤其是它们的分化特性。正如预期的那样,NSCs分化为成熟的神经表型。然而,在相同的分化条件下,BTSCs表现出明显的差异。形态学上,细胞在第一周生长扁平并附着,但此后逐渐聚集并重新形成漂浮的肿瘤球。在相应期间,BTSCs中未分化细胞标志物CD133和巢蛋白的表达率持续下降,但1周后,它们又恢复了上升趋势。有趣的是,分化细胞标志物GFAP和β-微管蛋白III的表达变化与未分化细胞标志物的表达变化相反。综上所述,BTSCs被揭示具有抵抗分化的能力,这实际上代表了胶质瘤的恶性行为。