title: 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 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.
authors.affiliation: Maxine Dunitz Neurosugical Institute, Los Angeles, California, USA.
authors.forename: Ali Jourabchi
authors.initials: AJ
authors.lastname: Ghods
authors.forename: Dwain
authors.initials: D
authors.lastname: Irvin
authors.forename: Gentao
authors.initials: G
authors.lastname: Liu
authors.forename: Xiangpeng
authors.initials: X
authors.lastname: Yuan
authors.forename: Iman R
authors.initials: IR
authors.lastname: Abdulkadir
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tunici
authors.forename: Bindu
authors.initials: B
authors.lastname: Konda
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wachsmann-Hogiu
authors.forename: Keith L
authors.initials: KL
authors.lastname: Black
authors.forename: John S
authors.initials: JS
authors.lastname: Yu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D019008:Drug Resistance, Neoplasm; D018316:Gliosarcoma / Q000473:pathology*; D008163:Luminescent Measurements; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor