Identification of a tumor-initiating stem cell population in human renal carcinomas
Identification of a tumor-initiating stem cell population in human renal carcinomas
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DOI：
10.1096/fj.08-102590
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发表时间：
2008-10-01
期刊：
影响因子：
4.8
通讯作者：
Camussi, Giovanni
中科院分区：
文献类型：
--
作者：
Bussolati, Benedetta;Bruno, Stefania;Camussi, Giovanni
本研究的目的是寻找肾癌中肿瘤启动干细胞群的存在。基于最近对正常肾脏间充质干细胞的鉴定，我们从5例人肾癌中筛选了表达间充质干细胞标记物CD105的细胞。由于CD105（+）而非CD105（-）群体在注射严重免疫缺陷（SCID）小鼠时表现出增强的致瘤性，我们克隆并表征了CD105（+）细胞，并评估了它们的干性、分化能力和连续肿瘤发生。CD105（+）克隆的表型表征揭示了几种干细胞特性：1)克隆生成能力，2)表达nestin， Nanog， Oct4干细胞标记物，缺乏分化上皮标记物，3)在非粘附球体中生长的能力，4)体外分化为上皮细胞和内皮细胞类型，以及5)在体内产生序列可移植癌，包含未分化的CD105（+）致瘤性和分化的CD105（-）非致瘤性群体。此外，在由CD105（+）克隆产生的癌中存在的一些血管是人类起源的，这表明肿瘤启动干细胞在内皮细胞中也具有体内分化的能力。总之，我们证明来自肾癌的CD105（+）细胞和克隆在具有干细胞特征的肿瘤启动细胞中富集。
The purpose of the present study was to search for the presence of a tumor-initiating stem cell population in renal carcinomas. Based on the recent identification of mesenchymal stem cells in normal kidneys, we sorted cells expressing the mesenchymal stem cell marker CD105 from 5 human renal carcinomas. Because the CD105(+) but not the CD105(-) population showed enhanced tumorigenicity when injected in severely compromised immunodeficient (SCID) mice, we cloned and characterized CD105(+) cells and evaluated their stemness, differentiative ability, and serial tumor generation. Characterization of the phenotype of CD105(+) clones revealed several stem cell properties: 1) clonogenic ability, 2) expression of nestin, Nanog, Oct4 stem cell markers, and lack of differentiative epithelial markers, 3) ability to grow in non-adhesive spheroids, 4) an vitro differentiation into epithelial and endothelial cell types, and 5) generation in vivo of serially transplantable carcinomas containing an undifferentiated CD105(+) tumorigenic and a differentiated CD105(-) nontumorigenic population. In addition, some vessels present in carcinomas generated from CD105(+) clones were of human origin, suggesting the capability of tumor-initiating stem cells to in vivo differentiate also in endothelial cells. In conclusion, we demonstrate that CD105(+) cells and clones derived from renal carcinomas were enriched in tumor-initiating cells with stem characteristics.