Glioblastoma multiforme is the most aggressive primary
tumor of the central nervous system.
Glioma stem cells (GSCs), a small population of
tumor cells with stem-like properties, are supposedly responsible for
glioblastoma multiforme relapse after current
therapies. In approximately thirty percent of
glioblastoma multiforme tumors, telomeres are not maintained by
telomerase but through an alternative mechanism, termed alternative lengthening of telomere (ALT), suggesting potential interest in developing specific therapeutic strategies. However, no preclinical model of ALT
glioma was available until the isolation of TG20 cells from a human ALT
glioma. Herein, we show that TG20 cells exhibit a high level of telomeric recombination but a stable karyotype, indicating that their telomeres retain their protective function against
chromosomal instability. TG20 cells possess all of the characteristic features of GSCs: the expression of neural stem cell markers, the generation of intracerebral
tumors in NOD-SCID-IL2Rγ (NSG) mice as well as in nude mice, and the ability to sustain serial intracerebral
transplantations without expressing
telomerase, demonstrating the stability of the ALT phenotype in vivo. Furthermore, we also demonstrate that 360B, a G-quadruplex
ligand of the
pyridine derivative series that impairs telomere replication and mitotic progression in
cancer cells, prevents the development of TG20
tumors. Together, our results show that intracerebral grafts of TG20 cells in immunodeficient mice constitute an efficient preclinical model of ALT
glioblastoma multiforme and that G-quadruplex
ligands are a potential
therapy for this specific type of
tumor.