TY - JOUR
T1 - Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells
AU - Ghods, Ali Jourabchi
AU - Irvin, Dwain
AU - Liu, Gentao
AU - Yuan, Xiangpeng
AU - Abdulkadir, Iman R.
AU - Tunici, Patrizia
AU - Konda, Bindu
AU - Wachsmann-Hogiu, Sebastian
AU - Black, Keith L.
AU - Yu, John S.
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Cancer stem-like cells
KW - Glioma
KW - Mitogens
KW - Monolayer
KW - Spheres
UR - http://www.scopus.com/inward/record.url?scp=34547197024&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547197024&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2006-0624
DO - 10.1634/stemcells.2006-0624
M3 - Article
C2 - 17412894
AN - SCOPUS:34547197024
VL - 25
SP - 1645
EP - 1653
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 7
ER -