Ghods Ali Jourabchi, Irvin Dwain, Liu Gentao, Yuan Xiangpeng, Abdulkadir Iman R, Tunici Patrizia, Konda Bindu, Wachsmann-Hogiu Sebastian, Black Keith L, Yu John S
Maxine Dunitz Neurosugical Institute, Los Angeles, California, USA.
Stem Cells. 2007 Jul;25(7):1645-53. doi: 10.1634/stemcells.2006-0624. Epub 2007 Apr 5.
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 antiapoptosis and drug-related genes, which may prove to have important clinical implications. Disclosure of potential conflicts of interest is found at the end of this article.
大鼠9L胶质肉瘤是一种广泛应用的同基因大鼠脑肿瘤模型，当植入体内时能紧密模拟多形性胶质母细胞瘤。在本研究中，我们试图从9L胶质肉瘤细胞系中分离并鉴定出一组癌症干细胞样细胞（CSLCs），它们可能代表肿瘤起始细胞亚群。我们证明，这些CSLCs在不含血清但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的培养基中形成克隆来源的球体，表达神经干细胞标志物巢蛋白和Sox2，具有自我更新能力，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，这些细胞植入同基因Fisher大鼠脑内时能够增殖并形成肿瘤，与在无有丝分裂原的单层培养中生长的9L胶质肉瘤细胞相比，它们呈现出更具侵袭性的病程。此外，我们比较了单层生长的9L胶质肉瘤细胞与悬浮球体生长的细胞的化学敏感性和增殖率，结果表明球体生成的细胞增殖率较低、对化疗更具抗性，并且表达几种抗凋亡和与药物相关的基因，这可能具有重要的临床意义。潜在利益冲突的披露见本文末尾。
