CTR2 鉴定出患有透明细胞肾细胞癌患者中具有干细胞样特征的癌细胞群体。

CTR2 identifies a population of cancer cells with stem cell-like features in patients with clear cell renal cell carcinoma.

机构信息

Andrology and Kidney Transplantation Unit, Department of Emergency and Organ Transplantation-Urology, University of Bari, Bari, Italy.

Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation-Nephrology, University of Bari, Bari, Italy.

出版信息

J Urol. 2014 Dec;192(6):1831-41. doi: 10.1016/j.juro.2014.06.070. Epub 2014 Jun 24.

DOI:10.1016/j.juro.2014.06.070

PMID:24972308

Abstract

PURPOSE

In clear cell renal cell carcinoma tissue samples we identified and characterized a population of renal cell carcinoma derived CD133+/CD24+ cancer cells. We studied differences between these cells and their nonneoplastic counterpart, tubular adult renal progenitor cells.

MATERIALS AND METHODS

CD133+/CD24+ renal cell carcinoma derived cells were isolated from 40 patients. The mesenchymal phenotype and stemness proteomic profile of these renal cell carcinoma derived cells were characterized. Colony forming efficiency and self-renewal ability were tested by limiting dilution. Tumorigenic properties were evaluated in vitro by soft agar assay. The angiogenic response was evaluated in vivo by the chorioallantoic membrane angiogenic assay. Microarray analysis was performed on 6 tubular adult renal progenitor cell and 6 renal cell carcinoma derived cell clones. Membrane protein expression was evaluated by flow cytometry and immunofluorescence staining.

RESULTS

CD133+/CD24+ cells were isolated from normal and tumor kidney tissue. Fluorescence activated cell sorting revealed that renal cell carcinoma derived cells did not express mesenchymal stem cell markers. CD133+/CD24+ tumor cells were more undifferentiated than tubular adult renal progenitor cells. Renal cell carcinoma derived cells were clonigenic and could differentiate into adipocytes, epithelial and osteogenic cells. They could also regenerate tumor cells in vitro and induce angiogenesis in vivo. Gene expression profile identified CTR2 as a membrane marker for this neoplastic population. CTR2 was involved in renal cell carcinoma derived cell cisplatin resistance.

CONCLUSIONS

Our results indicate the presence of a CD133+/CD24+/CTR2+ cancer cell population in clear cell renal cell carcinoma. These cells have some stem cell-like features, including in vitro self-maintenance and differentiating capabilities, and they can induce an angiogenic response in vivo.

摘要

目的

在透明细胞肾细胞癌组织样本中，我们鉴定并表征了一群源自肾细胞癌的 CD133+/CD24+癌细胞。我们研究了这些细胞与非肿瘤性的管状成人肾祖细胞之间的差异。

材料和方法

从 40 名患者中分离出 CD133+/CD24+肾癌细胞衍生细胞。对这些肾癌细胞衍生细胞的间充质表型和干性蛋白质组学特征进行了表征。通过有限稀释试验测试了集落形成效率和自我更新能力。通过软琼脂测定在体外评估了肿瘤发生特性。通过绒毛尿囊膜血管生成测定在体内评估了血管生成反应。对 6 个管状成人肾祖细胞和 6 个肾癌细胞衍生细胞克隆进行了微阵列分析。通过流式细胞术和免疫荧光染色评估了膜蛋白表达。

结果

从正常和肿瘤肾组织中分离出 CD133+/CD24+细胞。荧光激活细胞分选显示，肾癌细胞衍生细胞不表达间充质干细胞标志物。CD133+/CD24+肿瘤细胞比管状成人肾祖细胞更未分化。肾癌细胞衍生细胞具有克隆形成能力，并能分化为脂肪细胞、上皮细胞和成骨细胞。它们还可以在体外再生肿瘤细胞，并在体内诱导血管生成。基因表达谱确定 CTR2 为该肿瘤细胞群的膜标记物。CTR2 参与肾癌细胞衍生细胞顺铂耐药。