CD133、CD15/SSEA-1、CD34 或侧群细胞不能恢复人恶性神经胶质神经元肿瘤长期培养的肿瘤起始细胞的肿瘤起始特性。

BACKGROUND

Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies.

METHODS

We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas.

RESULTS

A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide.

CONCLUSIONS

Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.

背景

肿瘤起始细胞（TICs）为开发原始治疗策略提供了新的范例。

方法

我们在 47 个人类成人脑恶性肿瘤中筛选 TICs。从神经胶质瘤、髓母细胞瘤中获得了能够在培养中形成漂浮球体并具有预期的肿瘤细胞特征的细胞，但从少突胶质细胞瘤中没有获得。

结果

恶性神经胶质神经元肿瘤（MGNTs）的细胞表现出特别长的自我更新能力。细胞分选、核型分析和蛋白质组学分析表明，细胞在长时间传代中保持稳定。在裸鼠大脑中少于 500 个细胞的异种移植物诱导了逐渐生长的肿瘤。在形成球体的细胞亚群中出现 CD133、CD15/LeX/Ssea-1、CD34 的表达或排除 Hoechst 染料，但不能预测其形成次级球体或肿瘤的能力，或抵抗高剂量替莫唑胺的能力。