CD133-negative glioma cells form tumours, while the onset of CD133 expression coincides with angiogenesis and shortened survival

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA LB-91 ABSTRACT Recent work has identified CD133 as a marker of brain tumor-initiating cells. In this study, human glioblastoma biopsies were xenografted intracerebrally into nude rat brains. The resulting tumors expressed little or no CD133, and showed no contrast enhancement suggesting a normal vasculature with an intact blood-brain barrier. During serial passaging in vivo , the tumors gradually displayed more contrast enhancement. Real-time qPCR and immunoblots showed that this change was accompanied by increased angiogenesis, increased CD133 expression and a shorter survival. Biopsies were then dissociated and sorted by flow cytometry into CD133-negative and CD133-positive cell populations. Both populations incorporated BrdU in cell culture, expressed neural precursor markers, and were equally tumorigenic when implanted into the brains of immuno-deficient rats. Moreover, the implanted CD133-negative cells gave rise to tumors that contained CD133-positive cells. CD133 expression was also characterized in 6 tumorgenic glioma cell lines. Even though all the cell lines were tumorigenic, immunocytochemistry, flowcytometry qRT-PCR and immunoblotting showed no expression of CD133 on the tumor cells. >In conclusion, the work demonstrates that also CD133-negative tumour cells can initiate brain tumour formation with similar take rates as their CD133-positive counterparts. Moreover, CD133 expression coincides with the onset of angiogenesis and a shorter survival suggesting a role for CD133-positive cells in tumour angiogenesis.