Brain Tumor Stem Cell-Like Cells Highly Tumorigenic
Temozolomide treatment increases stem cell-like population
MONDAY, Mar. 9 (HealthDay News) -- A population of stem cell-like glioma cells characterized by the presence of a drug transporter are highly tumorigenic and resistant to drugs, and the standard glioma treatment increases this population, according to a report in the Mar. 6 issue of Cell Stem Cell.
Anne-Marie Bleau, Ph.D., and colleagues from Memorial Sloan-Kettering Cancer Center in New York City isolated and studied the side population (SP) cells, which are stem-like cells identified by their lack of staining with a fluorescent dye due to the presence of the drug efflux transporter ABCG2, from mouse and human gliomas.
The researchers found that ABCG2 function was impaired in glioma endothelial cells, consistent with a disruption of the blood brain barrier. In contrast, SP cells were enriched in non-endothelial cells, which were highly tumorigenic, could self-renew and were resistant to drugs. SP cells were also increased by temozolomide, the standard treatment for gliomas, even though it is not a substrate for ABCG2. Further investigation showed that a cellular signaling pathway regulated ABCG2 activity, thereby affecting the ability of the cells to expel drugs, and the SP.
"In summary, our studies support a role for ABCG2 as a molecular determinant of the side population phenotype in glioma stem-like cells, a phenotype characterized by both tumorigenic and chemoresistant properties," Bleau and colleagues conclude.