| Primary gliomas are a significant cause of mortality in both human and canine patients and conventional therapies including radiation, systemic chemotherapy and surgery have had limited impact on survival to date. Recently cumulative evidence has been presented in support of the cancer stem cell hypothesis, which postulates that within the heterogeneous tumor cell population only a small number of cells bearing stem cell properties are responsible for tumor progression. These cancer stem cells have been identified in a variety of human brain tumors and in a canine GBM. We set out to identify cancer stem cell populations in a variety of canine brain tumors through genomic and proteomic analysis of putative stem cell markers and further isolate and characterize these brain tumor stem cells (BTSCs) in vitro and in vivo. We found evidence for increased expression of putative stem cell markers Olig2 and CSPG4 (NG2), but not CD133, in canine gliomas compared to normal brain. In addition, canine glioma cells demonstrate the ability to alter expression of CD133, Olig2, and GFAP in a reversible manner, depending on culture conditions and environment. Furthermore, the expression of CD133 and Olig2 in glioma cells in vitro did not correlated with in vivo tumorigenic potential, although the ability to upregulate Olig2 may be critical for gliomagenesis. Based on a limited number of samples available for comparative in vitro and in vivo analysis, we did not find evidence for the existence of cells within canine brain tumors that fulfill the requirements of BTSCs. While the status of BTSCs in canine gliomas is yet unclear, these data support the idea that a least some canine glioma cells maintain a cellular plasticity that is normally lost upon differentiation of non-neoplastic brain cells. |
