Isolation and characterization of tumor stem-like cells from human meningiomas.
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.
Department of Neurological Surgery, Tri-Service General Hospital, Graduate Institute of Medical Sciences, National Defense Medical Center, 325, Sec. 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, ROC.
Dueng-Yuan
DY
Hueng
Huey-Kang
HK
Sytwu
Shih-Ming
SM
Huang
Chen
C
Chang
Hsin-I
HI
Ma
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008577:Meningeal Neoplasms / Q000473:pathology*; D008579:Meningioma / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011839:Radiation, Ionizing; D014750:Vincristine / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D014750:Vincristine