Spheres Isolated from 9L Gliosarcoma Rat Cell Line Possess Chemoresistant and Aggressive Cancer Stem‐Like Cells

Abstract

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 clonalderived 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.

Conditional Activation of Bmi1 Expression Regulates Self-renewal, Apoptosis, and Differentiation of Neural Stem/Progenitor Cells In Vitro and In Vivo

“…These cells express high levels of Bmi1 [30], are particularly resistant to apoptosis [31,32] and have recently been shown to be A2B5þ [33]. Overexpression of Bmi1 in postnatal SVZ NSPC in vitro led to increased self-renewal capacity as observed in embryonic NSPC.…”

HIF-1α is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway

“…9,36,37 These studies suggest that tumor sphere cells maybe a convenient and useful model for cancer stem cells research, although not every cell within tumor spheres is cancer stem cell. Here, we take U251SC, a U251 derived tumor sphere cells, as a GSC model.…”

Sox2 expression in breast tumours and activation in breast cancer stem cells

“…We base our conclusions in antibodybased assays, thus, looking specifically at the protein level to avoid pseudogene detection. As opposed to spheres derived from glioma cell lines (Ghods et al, 2007), only a few cells in the mammospheres were stained positive for Sox2, thus it is tempting to speculate that the tumour-initiating property resides in those cells. Further experiments will be needed to specifically isolate Sox2-positive cells and test their tumour generating ability.…”