Neurosphere Formation Is an Independent Predictor of Clinical Outcome in Malignant Glioma

Renewable neurosphere formation in culture is a defining characteristic of certain brain tumor initiating cells. This retrospective study was designed to assess the relationship among neurosphere formation in cultured human glioma, tumorigenic capacity, and patient clinical outcome. Tumor samples we...

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Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Ohio), 2009-04, Vol.27 (4), p.980-987
Main Authors: Laks, Dan R., Masterman‐Smith, Michael, Visnyei, Koppany, Angenieux, Brigitte, Orozco, Nicholas M., Foran, Ian, Yong, William H., Vinters, Harry V., Liau, Linda M., Lazareff, Jorge A., Mischel, Paul S., Cloughesy, Timothy F., Horvath, Steve, Kornblum, Harley I.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Animals
Brain Neoplasms - mortality
Brain Neoplasms - pathology
Brain tumor stem cell
Cancer
Cancer stem cell
Child
Female
Glioblastoma
Glioma - mortality
Glioma - pathology
Human glioma
Humans
Kaplan-Meier Estimate
Male
Mice
Mice, SCID
Middle Aged
Neoplastic Stem Cells - cytology
Neurosphere
Prognosis
Progression free survival
Retrospective Studies
Treatment Outcome
Tumor Cells, Cultured - cytology
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Summary:Renewable neurosphere formation in culture is a defining characteristic of certain brain tumor initiating cells. This retrospective study was designed to assess the relationship among neurosphere formation in cultured human glioma, tumorigenic capacity, and patient clinical outcome. Tumor samples were cultured in neurosphere conditions from 32 patients with glioma, including a subpopulation of 15 patients with primary glioblastoma. A subsample of renewable neurosphere cultures was xenografted into mouse brain to determine if they were tumorigenic. Our study shows that both renewable neurosphere formation and tumorigenic capacity are significantly associated with clinical outcome measures. Renewable neurosphere formation in cultured human glioma significantly predicted an increased hazard of patient death and more rapid tumor progression. These results pertained to both the full population of glioma and the subpopulation of primary glioblastoma. Similarly, there was a significant hazard of progression for patients whose glioma had tumorigenic capacity. Multivariate analysis demonstrated that neurosphere formation remained a significant predictor of clinical outcome independent of Ki67 proliferation index. In addition, multivariate analysis of neurosphere formation, tumor grade and patient age, demonstrated that neurosphere formation was a robust, independent predictor of glioma tumor progression. Although the lengthy duration of this assay may preclude direct clinical application, these results exemplify how neurosphere culture serves as a clinically relevant model for the study of malignant glioma. Furthermore, this study suggests that the ability to propagate brain tumor stem cells in vitro is associated with clinical outcome. STEM CELLS 2009;27:980–987
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.15