RR cells carry more stem-like features compared to RU cells.
It has been previously shown that CD133High GBM cells represent more stem-like brain tumor initiating cells (BTICs) than CD133Low GBM cells26.
Using a commercially available Sox2 reporter, we identified the novel RU/RR dichotomy in NB cells, with the small subset of RR cells being significantly more stem-like than RU cells.
They're endowed with very robust proliferative potential, and they give rise to other cancer cells and also to more stem-like cells," says Tuomas Tammela, a postdoc at the Koch Institute and lead author of the paper, which appears in the May 10 online edition of Nature.
We find that hypoxia promotes the self-renewal capability of the stem and non-stem population as well as promoting a more stem-like phenotype in the non-stem population with increased neurosphere formation as well as upregulation of important stem cell factors, such as OCT4, NANOG and c-MYC.
The above data suggest that exposure to anti-tumor T cell activity, induced endogenously or through DC vaccination, renders gene expression more stem-like in gliomas.
Despite globally homogeneous gene expression in classical GSCs, significantly higher heterogeneity within progenitor/differentiation genes was evident in more stem-like GBM from external sources (Fig. 6A).
Together, these findings suggest that strong anti-tumor T cell activity is sufficient to render gliomas more stem-like and to homogenize progenitor/differentiation gene expression.
GL26 exhibited more stem-like gene and protein expression (Figs. 1A; 2B; 3A, B; Fig. S2A), as well as GSC functions including cyclopamine sensitivity (Fig. 3C), chemoresistance (Fig. 4A, B), and enhanced tumorigenesis in wild-type hosts (Fig. 4C), after exposure to anti-tumor CTL activity derived from either endogenous or vaccine-induced T cell responses.
Our comparisons suggest that some tumors are more stem-like than others, with a corresponding worse prognosis.
