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鉴定横纹肌样脑膜瘤中 CD105(内皮糖蛋白)阳性的干细胞样细胞。

Identification of CD105 (endoglin)-positive stem-like cells in rhabdoid meningioma.

机构信息

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

J Neurooncol. 2012 Feb;106(3):505-17. doi: 10.1007/s11060-011-0705-3. Epub 2011 Sep 6.

Abstract

To investigate the tumor-initiating cells (TICs) in rhabdoid meningioma (RM), a population of CD105-positive cells isolated from a fresh RM surgical sample was analyzed for proliferative activity, self-renewal ability, tumorigenic ability, multilineage differentiation potential, as well as chromosomal aberrations. The results showed that isolated CD105-positive cells could be maintained for more than 50 generations in vitro. These cells exhibited increased proliferative activity and single-cell tumor sphere-formation ability compared with CD105-negative cells. In vivo experiments showed that CD105-positive cells possessed much greater potential to reconstitute the original human RM in nude mice as compared with CD105-negative cells. Phenotypically, CD105-positive cells shared some surface markers with mesenchymal progenitor cells (MPCs), but karyotype analysis showed chromosomal abnormalities characteristic of malignant meningioma, thus distinguishing them from supportive stroma-derived MPCs. In addition, in contrast to CD105-negative cells, CD105-positive cells could differentiate into adipocytes and osteocytes in response to specific induction agents. Finally, CD105-positive cells with stem-like features were also isolated from xenograft tumors. In conclusion, a population of CD105-positive TICs with some traits of MPCs was identified in RM and might provide a promising therapeutic target in management of malignant meningioma.

摘要

为了研究横纹肌样脑膜瘤(rhabdoid meningioma,RM)中的肿瘤起始细胞(tumor-initiating cells,TICs),我们分析了从新鲜 RM 手术样本中分离的 CD105 阳性细胞的增殖活性、自我更新能力、致瘤能力、多能分化潜能以及染色体畸变。结果表明,分离的 CD105 阳性细胞在体外可维持超过 50 代。与 CD105 阴性细胞相比,这些细胞表现出更高的增殖活性和单细胞肿瘤球体形成能力。体内实验表明,与 CD105 阴性细胞相比,CD105 阳性细胞在裸鼠中具有更大的潜力重建原始人 RM。表型上,CD105 阳性细胞与间充质祖细胞(mesenchymal progenitor cells,MPCs)具有一些表面标记物,但核型分析显示出恶性脑膜瘤特有的染色体异常,从而将其与支持基质衍生的 MPCs 区分开来。此外,与 CD105 阴性细胞相比,CD105 阳性细胞在特定诱导剂的作用下可分化为脂肪细胞和成骨细胞。最后,在异种移植肿瘤中也分离到了具有干细胞样特征的 CD105 阳性细胞。总之,在 RM 中鉴定出了一群具有 MPC 某些特征的 CD105 阳性 TICs,这可能为恶性脑膜瘤的治疗提供有希望的靶点。

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