A way to understand idiopathic senescence and apoptosis in primary glioblastoma cells - possible approaches to circumvent these phenomena

• Published in: BMC cancer Vol. 19; no. 1; p. 923
• Main Authors: Janik, Karolina, Treda, Cezary, Wlodarczyk, Aneta, Peciak, Joanna, Rosiak, Kamila, Zieba, Jolanta, Grot, Dagmara, Rutkowska, Adrianna, Pawlowska, Roza, Och, Waldemar, Rieske, Piotr, Stoczynska-Fidelus, Ewelina
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.09.2019; BioMed Central; BMC
• Subjects: Aging (Biology); Animals; Apoptosis; Apoptosis - genetics; Bioethics; Brain cancer; Brain Neoplasms - etiology; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; Cancer; Care and treatment; Cell culture; Cell cycle; Cell death; Cell Line, Tumor; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cellular Senescence - genetics; EDTA; Gene Expression Profiling; Genetic aspects; Genotype; Glioblastoma; Glioblastoma - etiology; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma cells; Glioblastomas; Glioma; Gliomas; Humans; Immortalization; In vivo model; Mice; Mutation; Neural stem cells; Phenotype; Proteins; Senescence; Stem cell transplantation; Stem cells; Tumors; In vivo model; Senescence; Immortalization; Glioblastoma; Apoptosis
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-6130-2

Glioblastoma (GB) is considered one of the most lethal tumors. Extensive research at the molecular level may enable to gain more profound insight into its biology and thus, facilitate development and testing of new therapeutic approaches. Unfortunately, stable glioblastoma cell lines do not reflect highly heterogeneous nature of this tumor, while its primary cultures are difficult to maintain in vitro. We previously reported that senescence is one of the major mechanisms responsible for primary GB cells stabilization failure, to a lesser extent accompanied by apoptosis and mitotic catastrophe-related cell death. We made an attempt to circumvent difficulties with glioblastoma primary cultures by testing 3 different approaches aimed to prolong their in vitro maintenance, on a model of 10 patient-derived tumor specimens. Two out of ten analyzed GB specimens were successfully stabilized, regardless of culture approach applied. Importantly, cells transduced with immortalizing factors or cultured in neural stem cell-like conditions were still undergoing senescence/apoptosis. Sequential in vivo/in vitro cultivation turned out to be the most effective, however, it only enabled to propagate cells with preserved molecular profile up to 3 mice transfer. Nevertheless, it was the only method that impeded these phenomena long enough to provide sufficient amount of material for in vitro/in vivo targeted analyses. Interestingly, our data additionally demonstrated that some subpopulations of several stabilized GB cell lines undergo idiopathic senescence, however, it is counterbalanced by simultaneous proliferation of other cell subpopulations. In the majority of primary glioma cultures, there has to be an imbalance towards apoptosis and senescence, following few weeks of rapid proliferation. Our results indicate that it has to be associated with the mechanisms other than maintenance of glioblastoma stem cells or dependence on proteins controlling cell cycle.