Testing oncolytic activity of human enteroviruses against glioblastoma-initiating cancer stem cells.
Glioblastomas (GBMs) are highly lethal primary brain tumors. GBMs are extremely resistant to conventional radiation and chemotherapies. A highly tumorigenic subpopulation of cancer cells, the GBM stem cells (GSCs) is the major cause of resistance to radio- and chemotherapy.
Oncolityc viruses (OV) are considered as perspective agents for anticancer therapy. OVs are capable of selective replication and killing of cancer cells by spreading through the tumor mass, without damaging normal tissue. The OVs are believed to be capable of overcoming the problem of cancer stem cells resistance by efficiently targeting GSCs. In this study we tested oncolytic effects mediated by some strains of human enteroviruses.
We analyzed tumor cells from primary and model glioblastomas cell line that had been cultured in a medium promoting the growth of CSCs. To estimate cancer stem cells level in patient-derived glioblastoma cell lines we used lentiviral-based reporter system that allows direct visualization of CSCs based on functional properties. We also measured cancer stem cell count in established lines by the ALDEFLUOR assay. Increased aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been found in the stem cell populations of leukemia and some solid tumors. We found an efficient killing of glioblastoma CSCs after treatment with some strains of oncolytic enteroviruses.