Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells
Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells
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DOI：
10.1634/stemcells.2006-0624
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发表时间：
2007-07-01
期刊：
影响因子：
5.2
通讯作者：
Yu, John S.
中科院分区：
文献类型：
--
作者：
Ghods, Ali Jourabcih;Irvin, Dwain;Yu, John S.
大鼠9L胶质肉瘤是一种广泛使用的同基因大鼠脑肿瘤模型，与体内移植的多形性胶质母细胞瘤非常相似。在这项研究中，我们试图从9L胶质肉瘤细胞系中分离和鉴定一组癌症干细胞(CSLC)，这可能代表了肿瘤启动细胞的亚群。我们证明这些CSLC在无血清的条件下形成克隆衍生的球体，在无血清的条件下添加有丝分裂原表皮生长因子和碱性成纤维细胞生长因子，表达NSC标志物Nestin和Sox2，自我更新，并在体外分化为神经元样细胞和神经胶质细胞。更重要的是，当这些细胞移植到同基因Fisher大鼠的大脑中时，它们可以增殖和重现肿瘤，并且与在没有丝裂原的单层培养中生长的9L胶质肉瘤细胞相比，它们表现出更具侵袭性的过程。此外，我们还比较了单层生长的9L胶质肉瘤细胞和漂浮球体生长的细胞对化疗的敏感性和增殖率，结果表明，球体生长的细胞增殖率较低，对化疗的抵抗力更强，并表达多种抗细胞凋亡和药物相关基因，这可能被证明具有重要的临床意义。
The rat 9L gliosarcoma is a widely used syngeneic rat brain tumor model that closely simulates glioblastoma multiforme when implanted in vivo. In this study, we sought to isolate and characterize a subgroup of cancer stem-like cells (CSLCs) from the 9L gliosarcoma cell line, which may represent the tumor-initiating subpopulation of cells. We demonstrate that these CSLCs form clonal-derived spheres in media devoid of serum supplemented with the mitogens epidermal growth factor and basic fibroblast growth factor, express the NSC markers Nestin and Sox2, self-renew, and differentiate into neuron-like and glial cells in vitro. More importantly, these cells can propagate and recapitulate tumors when implanted into the brain of syngeneic Fisher rats, and they display a more aggressive course compared with 9L gliosarcoma cells grown in monolayer cultures devoid of mitogens. Furthermore, we compare the chemosensitivity and proliferation rate of 9L gliosarcoma cells grown as a monolayer to those of cells grown as floating spheres and show that the sphere-generated cells have a lower proliferation rate, are more chemoresistant, and express several antia-poptosis and drug-related genes, which may prove to have important clinical implications.