Stmc-14. glioblastoma cancer stem cells undergo dynamic state transitions

Glioblastoma (GBM) is a highly malignant brain tumor where no curative treatment is available. According to the cancer stem cell (CSC) hypothesis GBMs rely on a small subpopulation of cancer cells with stem-like properties responsible for tumor progression and recurrence. Recent experimental data from GBM and other cancers however suggest that CSCs cannot be defined by specific marker expression and may in fact not be a stable entity but a population of cells adapting to a changing microenvironment. We have previously shown that glioma CSCs do not represent a genetically homogenous population. Here we examined inter- and intra-tumoral heterogeneity of CSCs and their adaptation capacity based on stem cell-associated marker expression profiles. Tumor cell subpopulations were classified based on their expression of four chosen cell membrane markers (CD133, CD15, A2B5 and CD44) using multicolor flow cytometry. 16 subpopulations were separated and analyzed for their self-renewal capacity and their ability to reform the original heterogeneous cell population. Mathematical modelling was applied to calculate state transitions between phenotypes and predict the adaptive response of CSCs. Similar to GBM biopsies, we observed markers to be heterogeneously expressed in glioma stem-like cells and primary cultures. All analyzed tumor cell subpopulations were able to proliferate and carried stem-cell properties including self-renewal potential. Moreover all subpopulations were able to adapt...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: STEM CELLS Source Type: research