Isolation and characterization of tumor stem-like cells from human meningiomas
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Recent advances in research have found that tumor stem-like cells are resistant to surgery, radiotherapy, and chemotherapy. Tumor stem-like cells play critical roles in tumor recurrence, angiogenesis, and invasion in malignant brain tumors. However, the identification of tumor stem-like cells in meningiomas has not been clarified. In this study, we identified the stem-like features of sphere-forming cells in human meningiomas. The results showed that meningioma stem-like cells possess the ability to form spheres in identical stem cell culture condition. These meningioma sphere cells (MgSCs) expressed progenitor cell marker, CD133, but not differentiated cell marker, epithelial membrane antigen (EMA) on immunofluorescence staining. Importantly, the mRNA expression of ABCG, and CD133 was higher in MgSCs than daughter meningioma adherent cells (MgACs). In addition, cells displayed chemotherapeutic resistance to vincristine more in MgSCs than MgACs. This phenomenon was also found in single cell form from dissociated spheres than MgACs. Moreover, MgSCs are more resistant to irradiation treatment than MgACs. Furthermore, MgSCs revealed high tumorigenicity in vivo following orthotopic inoculation into the brains of immunodeficient mice. The corresponding immunohistochemical (IHC) staining found that MgSCs are positive for EMA, vimentin, and CD133, consistent with IHC of primary human meningiomas. These findings have provided better understanding of meningioma cell biology and suggested that meningioma stem-like cells may serve as a novel target in therapeutic resistant meningiomas.
KeywordsCD133 Chemoresistance Meningioma Radioresistance Sphere Tumor stem-like cell
This study was supported by grants TSGH-C99-069, TSGH-C99-072, TSGH-C99-073, TSGH-C99-074, and TSGH-C99-149, from the Tri-Service General Hospital (D.-Y. Hueng), NSC-96-2628-B-016-002-MY3, NSC98-3112-B-016-002 and NSC99-3112-B-016-001 (H.-K. Sytwu), and a grant B971113 from the Teh-Tzer Study Group for Human Medical Research Foundation, and grants DOH99-TD-B-111-003, and DOH99-TD-C-111-008, from Taiwan Department of Health for the Center of Excellence for Clinical Trial and Research in Neuroscience, and the Center of Excellence for Cancer Research.
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