Different mutational characteristics of TSG in cell lines and surgical specimens

Stoczyńska-Fidelus, Ewelina; Bieńkowski, Michał; Pacholczyk, Marcin; Winiecka-Klimek, Marta; Banaszczyk, Mateusz; Zieba, Jolanta; Bieniek, Grzegorz; Piaskowski, Sylwester; Rieske, Piotr

doi:10.1007/s13277-014-2444-5

Cited by 2 publications

(2 citation statements)

References 17 publications

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“… 11 , 14 One study has reported the tumorigenicity of cells from a primary gliosarcoma at early passage in serum condition, and some commercially available glioma cell lines are tumorigenic in serum condition, but these cell lines were criticized recently. 15 , 16 , 17 Another widely used method for enrichment of GSCs is cell sorting based on CD133 expression. 2 , 18 However, this is not a reliable method as some CD133-negative cells can also be tumorigenic, and some fresh and in vitro -expanded GBM specimens do not express CD133.…”

Section: Introductionmentioning

confidence: 99%

Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency

et al. 2016

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Glioblastoma Multiforme (GBM) is characterized by high cancer cell heterogeneity and the presence of a complex tumor microenvironment. Those factors are a key obstacle for the treatment of this tumor type. To model the disease in mice, the current strategy is to grow GBM cells in serum-free non-adherent condition, which maintains their tumor-initiating potential. However, the so-generated tumors are histologically different from the one of origin. In this work, we performed high-throughput marker expression analysis and investigated the tumorigenicity of GBM cells enriched under different culture conditions. We identified a marker panel that distinguished tumorigenic sphere cultures from non-tumorigenic serum cultures (high CD56, SOX2, SOX9, and low CD105, CD248, αSMA). Contrary to previous work, we found that ‘mixed cell cultures' grown in serum conditions are tumorigenic and express cancer stem cell (CSC) markers. As well, 1% serum plus bFGF and TGF-α preserved the tumorigenicity of sphere cultures and induced epithelial-to-mesenchymal transition gene expression. Furthermore, we identified 12 genes that could replace the 840 genes of The Cancer Genome Atlas (TCGA) used for GBM-subtyping. Our data suggest that the tumorigenicity of GBM cultures depend on cell culture strategies that retain CSCs in culture rather than the presence of serum in the cell culture medium.

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Section: Introductionmentioning

confidence: 99%

Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency

et al. 2016

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“…Moreover, we have previously described that there is a higher frequency of homozygous mutations in tumor suppressors as well as mutations resulting in lack of tumor suppressor proteins in cell lines when compared to surgical samples. Hence, there seems to be a complete loss of function of tumor suppressor genes in time [23]. On the other hand, mesenchymal GB subtype is suggested to be more prone to stabilization, even if patient was diagnosed with another GB subtype [16], what seems to be reasonable, as cells in monolayer conditions attach to the culture vessel and compete with normal stromal cells [24].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Background 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. Methods 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. Results 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 3rd 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. Conclusions 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.

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Different mutational characteristics of TSG in cell lines and surgical specimens

Cited by 2 publications

References 17 publications

Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency

Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency

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

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