HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0624v1 2006-0624v2 2006-0624v3 25/7/1645    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ghods, A. J. Articles by Yu, J. S. Search for Related Content PubMed PubMed Citation Articles by Ghods, A. J. Articles by Yu, J. S.

CANCER STEM CELLS

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

^aMaxine Dunitz Neurosurgical Institute, Los Angeles, California, USA;
^bDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA

Key Words. Spheres • Monolayer • Mitogens • Cancer stem-like cells • Glioma

Correspondence: John S. Yu, M.D., 8631 West Third Street, Suite 800E, Los Angeles, California 90048, USA. Telephone: 310-423-0845; Fax: 310-423-0810; e-mail: Yuj{at}cshs.org

Received October 2, 2006; accepted for publication March 29, 2007.
First published online in STEM CELLS EXPRESS   April 5, 2007.



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.