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人类实体瘤中CD133+癌症干细胞的检测与特性分析

Detection and characterization of CD133+ cancer stem cells in human solid tumours.

作者信息

Tirino Virginia, Desiderio Vincenzo, d'Aquino Riccardo, De Francesco Francesco, Pirozzi Giuseppe, Graziano Antonio, Galderisi Umberto, Cavaliere Carlo, De Rosa Alfredo, Papaccio Gianpaolo, Giordano Antonio

机构信息

Dipartimento di Medicina Sperimentale, Sezione di Istologia ed Embriologia, Seconda Università degli Studi di Napoli, Napoli, Italy.

出版信息

PLoS One. 2008;3(10):e3469. doi: 10.1371/journal.pone.0003469. Epub 2008 Oct 21.

Abstract

BACKGROUND

Osteosarcoma is the most common primary tumour of bone. Solid tumours are made of heterogeneous cell populations, which display different goals and roles in tumour economy. A rather small cell subset can hold or acquire stem potentials, gaining aggressiveness and increasing expectancy of recurrence. The CD133 antigen is a pentaspan membrane glycoprotein, which has been proposed as a cancer stem cell marker, since it has been previously demonstrated to be capable of identifying a cancer initiating subpopulation in brain, colon, melanoma and other solid tumours. Therefore, our aim was to observe the possible presence of cells expressing the CD133 antigen within solid tumour cell lines of osteosarcoma and, then, understand their biological characteristics and performances.

METHODOLOGY AND PRINCIPAL FINDINGS

In this study, using SAOS2, MG63 and U2OS, three human sarcoma cell lines isolated from young Caucasian subjects, we were able to identify and characterize, among them, CD133+ cells showing the following features: high proliferation rate, cell cycle detection in a G2\M phase, positivity for Ki-67, and expression of ABCG2 transporters. In addition, at the FACS, we were able to observe the CD133+ cell fraction showing side population profile and forming sphere-clusters in serum-free medium with a high clonogenic efficiency.

CONCLUSIONS

Taken together, our findings lead to the thought that we can assume that we have identified, for the first time, CD133+ cells within osteosarcoma cell lines, showing many features of cancer stem cells. This can be of rather interest in order to design new therapies against the bone cancer.

摘要

背景

骨肉瘤是最常见的原发性骨肿瘤。实体瘤由异质性细胞群体组成,这些细胞群体在肿瘤生物学中表现出不同的目标和作用。相当小的细胞亚群可以拥有或获得干细胞潜能,从而增强侵袭性并增加复发几率。CD133抗原是一种五跨膜糖蛋白,已被提议作为癌症干细胞标志物,因为先前已证明它能够识别脑、结肠、黑色素瘤和其他实体瘤中的癌症起始亚群。因此,我们的目的是观察骨肉瘤实体瘤细胞系中表达CD133抗原的细胞的可能存在情况,然后了解它们的生物学特性和表现。

方法和主要发现

在本研究中,我们使用从年轻白种人受试者中分离出的三种人类肉瘤细胞系SAOS2、MG63和U2OS,能够在其中鉴定和表征CD133 +细胞,这些细胞具有以下特征:高增殖率、细胞周期检测处于G2\M期、Ki-67阳性以及ABCG2转运蛋白的表达。此外,在流式细胞仪上,我们能够观察到CD133 +细胞部分呈现侧群细胞特征,并在无血清培养基中形成具有高克隆效率的球形簇。

结论

综上所述,我们的研究结果使我们认为,我们首次在骨肉瘤细胞系中鉴定出了具有许多癌症干细胞特征的CD133 +细胞。这对于设计针对骨癌的新疗法可能具有相当大的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99df/2565108/7f7aa43eda9b/pone.0003469.g001.jpg

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