Enhanced invasion in vitro and the distribution patterns in vivo of CD133+ glioma stem cells

Background Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistanceto radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma cells is also implicated in thefailure of current therapies, it is not clear whether cancer stem cells are involved in invasiveness. This study aimed toassess invasive ability of glioma stem cells （GSCs） derived from C6 glioma cell line and the distribution patterns of GSCsin Sprague-Dawley （SD） rat brain tumor.Methods Serum-free medium culture and magnetic isolation were used to gain purely CD133GSCs. The invasiveability of CD133and CD133C6 cells were determined using matrigel invasion assay. Immunohistochemical staining forstem cell markers and luxol fast blue staining for white matter tracts were performed to show the distribution patterns ofGSCs in brain tumor of rats and the relationship among GSCs, vessels, and white matter tracts. The results of matrigelinvasion assay were estimated using the Student’s f test and the analysis of Western blotting was performed using theone-way analysis of variance （ANOVA） test.Results CD133GSCs （number: 85.3±4.0） were significantly more invasive in vitro than matched CD133cells（number: 25.9±3.1） （t=14.5, P<0.005）. GSCs invaded into the brain diffusely and located in perivascular niche oftumor-brain interface or resided within perivascular niche next to white fiber tracts. The polarity of glioma cells containingGSCs was parallel to the white matter tracts.Conclusions Our data suggest that CD133GSCs exhibit more aggressive invasion in vitro and GSCs in vivo probablydisseminate along the long axis of blood vessels and transit through the white matter tracts. The therapies targetingGSCs invasion combined with traditional glioblastoma multiforme therapeutic paradigms might be a new approach foravoiding malignant glioma recurrence.