hTERT Transduction Extends the Lifespan of Primary Pediatric Low-Grade Glioma Cells While Preserving the Biological Response to NGF

Franzese, Ornella; Francesco, Angela Maria Di; Meco, Daniela; Graziani, Grazia; Cusano, Gabriella; Levati, Lauretta; Riccardi, Riccardo; Ruggiero, Antonio

doi:10.3389/pore.2021.612375

Cited by 5 publications

(5 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Primary LGG cells exhibit a notably low proliferative rate, limited to a finite number of divisions in culture, after which the cells enter a phase of growth arrest and initiate replicative senescence. This senescence program is triggered by an aberrant activation of the MAPK pathway, a hallmark feature of these tumors, and of the p16 pathway 41 . Hence, late-passage LGG cells may not faithfully represent the authentic tumor cells that undergo senescence.…”

Section: Discussionmentioning

confidence: 99%

Evaluating cell culture reliability in pediatric brain tumor primary cells through DNA methylation profiling

Pedace,

Pizzi,

Abballe

et al. 2024

npj Precis. Onc.

View full text Add to dashboard Cite

In vitro models of pediatric brain tumors (pBT) are instrumental for better understanding the mechanisms contributing to oncogenesis and testing new therapies; thus, ideally, they should recapitulate the original tumor. We applied DNA methylation (DNAm) and copy number variation (CNV) profiling to characterize 241 pBT samples, including 155 tumors and 86 pBT-derived cell cultures, considering serum vs serum-free conditions, late vs early passages, and dimensionality (2D vs 3D cultures). We performed a t-SNE classification and identified differentially methylated regions in tumors compared to cell models. Early cell cultures recapitulate the original tumor, but serum media and 2D culturing were demonstrated to significantly contribute to the divergence of DNAm profiles from the parental ones. All divergent cells clustered together acquiring a common deregulated epigenetic signature suggesting a shared selective pressure. We identified a set of hypomethylated genes shared among unfaithful cells converging on response to growth factors and migration pathways, such as signaling cascade activation, tissue organization, and cellular migration. In conclusion, DNAm and CNV are informative tools that should be used to assess the recapitulation of pBT-cells from parental tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluating cell culture reliability in pediatric brain tumor primary cells through DNA methylation profiling

Pedace,

Pizzi,

Abballe

et al. 2024

npj Precis. Onc.

View full text Add to dashboard Cite

show abstract

“…The overexpression of hTERT (human telomerase reverse transcriptase, the catalytic subunit of telomerase) was proposed to counteract OIS in pLGG cell lines so they regain their proliferative potential for long-term cultures [ ( 55 ), Figure 2 )]. Another method to extend lifespan of pLGG cell lines was proposed by Yuan et al.…”

Section: In Vitro Models Of Plgg: the Path To Establishing P...mentioning

confidence: 99%

“…Third, the intrinsic slow growth and benign behavior of these tumors coupled with OIS made it difficult to grow these tumor cells in vitro ( 48 , 49 , 52 , 54 , 60 ). Several methods were developed to bypass OIS through genetic modifications of the pLGG cells so that they can be propagated long enough in culture ( 53 , 55 ), but these methods might generate in vitro model systems that incompletely reflect the genetic/epigenetic background of the primary tumors. Nevertheless, as more research is being done into developing different ways to extend the lifespan of pLGG cells in vitro , certain methods such as conditional reprogramming culture conditions or using hIPSC-derived hINPCs might provide plausible solutions to generating viable in vitro models ( 56 , 68 ).…”

Section: Leveraging the Strengths And Overcoming The Challenges Of Ge...mentioning

confidence: 99%

Pediatric low-grade glioma models: advances and ongoing challenges

Yvone,

Breunig

2024

Front. Oncol.

View full text Add to dashboard Cite

Pediatric low-grade gliomas represent the most common childhood brain tumor class. While often curable, some tumors fail to respond and even successful treatments can have life-long side effects. Many clinical trials are underway for pediatric low-grade gliomas. However, these trials are expensive and challenging to organize due to the heterogeneity of patients and subtypes. Advances in sequencing technologies are helping to mitigate this by revealing the molecular landscapes of mutations in pediatric low-grade glioma. Functionalizing these mutations in the form of preclinical models is the next step in both understanding the disease mechanisms as well as for testing therapeutics. However, such models are often more difficult to generate due to their less proliferative nature, and the heterogeneity of tumor microenvironments, cell(s)-of-origin, and genetic alterations. In this review, we discuss the molecular and genetic alterations and the various preclinical models generated for the different types of pediatric low-grade gliomas. We examined the different preclinical models for pediatric low-grade gliomas, summarizing the scientific advances made to the field and therapeutic implications. We also discuss the advantages and limitations of the various models. This review highlights the importance of preclinical models for pediatric low-grade gliomas while noting the challenges and future directions of these models to improve therapeutic outcomes of pediatric low-grade gliomas.

show abstract

“…In the CNS, NGF is secreted predominantly in the cortex, hippocampus and pituitary gland ( 59 ). The specific NGF receptors TrkA and p75 NTR have been indicated to be expressed in gliomas ( 60 ). The effects of NGF on glioma cells, however, appear to be somewhat paradoxical.…”

Section: Neuronal Regulation In Glioma Progressionmentioning

confidence: 99%

Glioma‑neuronal interactions in tumor progression: Mechanism, therapeutic strategies and perspectives (Review)

et al. 2022

View full text Add to dashboard Cite

An increasing body of evidence has become available to reveal the synaptic and functional integration of glioma into the brain network, facilitating tumor progression. The novel discovery of glioma-neuronal interactions has fundamentally challenged our understanding of this refractory disease. The present review aimed to provide an overview of how the neuronal activities function through synapses, neurotransmitters, ion channels, gap junctions, tumor microtubes and neuronal molecules to establish communications with glioma, as well as a simplified explanation of the reciprocal effects of crosstalk on neuronal pathophysiology. In addition, the current state of therapeutic avenues targeting critical factors involved in glioma-euronal interactions is discussed and an overview of clinical trial data for further investigation is provided. Finally, newly emerging technologies, including immunomodulation, a neural stem cell-based delivery system, optogenetics techniques and co-culture of neuron organoids and glioma, are proposed, which may pave a way towards gaining deeper insight into both the mechanisms associated with neuron-and glioma-communicating networks and the development of therapeutic strategies to target this currently lethal brain tumor.

show abstract

hTERT Transduction Extends the Lifespan of Primary Pediatric Low-Grade Glioma Cells While Preserving the Biological Response to NGF

Cited by 5 publications

References 54 publications

Evaluating cell culture reliability in pediatric brain tumor primary cells through DNA methylation profiling

Evaluating cell culture reliability in pediatric brain tumor primary cells through DNA methylation profiling

Pediatric low-grade glioma models: advances and ongoing challenges

Glioma‑neuronal interactions in tumor progression: Mechanism, therapeutic strategies and perspectives (Review)

Contact Info

Product

Resources

About