Aggressive invasion is observed in CD133(−)/A2B5(+) glioma-initiating cells

Glioblastoma multiforme is the most common and fatal primary brain tumor in adults. Aggressive invasion of glioblastoma cells into brain tissue often limits complete surgical resection and contributes to therapeutic resistance. The cell surface marker, CD133, has been identified as a putative stem cell marker in normal and malignant brain tissues; CD133(−)/A2B5(+) cells exhibit neural stem-like cell properties. The invasive properties and the molecular mechanisms of CD133(−)/A2B5(+) glioma-initiating cells (GICs) were investigated in the process of self-renewal and tumorigenesis. An increased number of invasive cells through matrigel and an increase in migratory cells through filters were observed in CD133(−)/A2B5(+) GIC populations compared with matched non-initiating tumor cell populations. Considerable changes were detected in expression of mRNA and protein associated with migration or invasion. CD133(−)/A2B5(+) GIC demonstrated infiltrating growth patterns and displayed greater invasive potential under fluorescent microscopy comparing with the matched non-initiating tumor cells after cells labeled with red fluorescence protein were transplanted into the brains of athymic/nude mice. CD133(−)/A2B5(+) GICs possess strong migratory and invasive capacity. These infiltrating cells in the invasive fronts may be responsible for rapid tumor recurrence following conventional treatments. CD133(−)/A2B5(+) GICs may be an important subpopulation with high invasive potential and they should not be ignored when targeting GICs to prevent GBM recurrence.