Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells

Ali Jourabchi Ghods, Dwain Irvin, Gentao Liu, Xiangpeng Yuan, Iman R. Abdulkadir, Patrizia Tunici, Bindu Konda, Sebastian Wachsmann-Hogiu, Keith L. Black, John S. Yu

Research output: Contribution to journalArticle

121 Scopus citations

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 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 anti-apoptosis and drug-related genes, which may prove to have important clinical implications.

Original languageEnglish (US)
Pages (from-to)1645-1653
Number of pages9
JournalStem Cells
Volume25
Issue number7
DOIs
StatePublished - Jul 2007

Keywords

  • Cancer stem-like cells
  • Glioma
  • Mitogens
  • Monolayer
  • Spheres

ASJC Scopus subject areas

  • Cell Biology

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    Ghods, A. J., Irvin, D., Liu, G., Yuan, X., Abdulkadir, I. R., Tunici, P., Konda, B., Wachsmann-Hogiu, S., Black, K. L., & Yu, J. S. (2007). Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells. Stem Cells, 25(7), 1645-1653. https://doi.org/10.1634/stemcells.2006-0624