CD133-negative glioblastoma cancer stem cells represent the ‘mesenchymal’ subclass of glioblastoma

3786 Whether CD133-positive (CD133 (+) ) cells are the only cancer stem cells of glioblastoma (GBM) is a hot issue these days. We isolated CD133 (+) and CD133-negative (CD133 (-) ) cells from one GBM patient (total 6 GBM patients) and found that both can produce tumor mass in the mouse brain. However, tumor masses produced by CD133 (-) cells had more vessels and PCNA-positive proliferating cells. Akt was activated more in the tumor masses produced by CD133 (+) cells. These results suggested that there are cancer stem cells in CD133 (-) cell population, however, they have different characteristics compared with CD133 (+) cells. To analyze different characteristics of CD133 (-) cells further, we gathered 20 GBM patients, analyzed their CD133 (+) cell ratios using FACS analysis method and divided them into two groups according to CD133 (+) cell ratio (CD133 (+) cell ratio high (≥3%, n=10) and low ( (+) tumors were observed as cortical and well-demarkcated tumors, while low CD133 (+) tumors were deep seated, periventricular tumors with more invasive growth patters (p (+) cell ratio extremely high (≥20%, n=4) and extremely low ( (+) GBMs have gene expressional characteristics similar with the ‘proneuronal to proliferative’ subclass of GBM and extremely low CD133 (-) GBMs showed ‘mesenchymal’ subclass-like gene expression profile which has the worst clinical outcome. Regarding these data, it can be concluded that there are at least two kinds of GBM cancer stem cell and that they represent different subclasses of GBM.