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

The neurotrophin nerve growth factor (NGF) modulates the growth of human gliomas and is able to induce cell differentiation through the engagement of tropomyosin receptor kinase A (TrkA) receptor, although the role played in controlling glioma survival has proved controversial. Unfortunately, the sl...

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Bibliographic Details
Published in:Pathology oncology research 2021-04, Vol.27, p.612375-612375
Main Authors: Franzese, Ornella, Di Francesco, Angela M, Meco, Daniela, Graziani, Grazia, Cusano, Gabriella, Levati, Lauretta, Riccardi, Riccardo, Ruggiero, Antonio
Format: Article
Language:English
Subjects:
Apoptosis
Brain cancer
Brain Neoplasms
Cell culture
Cell Culture Techniques - methods
Cell growth
Genomes
Glioma
Humans
Kinases
Medical prognosis
Mutation
Nerve Growth Factor - metabolism
Pediatrics
Senescence
Society Journal Archive
Telomerase
Telomerase - genetics
Transduction, Genetic - methods
Tumor Cells, Cultured
Tumors
Wound healing
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Summary:The neurotrophin nerve growth factor (NGF) modulates the growth of human gliomas and is able to induce cell differentiation through the engagement of tropomyosin receptor kinase A (TrkA) receptor, although the role played in controlling glioma survival has proved controversial. Unfortunately, the slow growth rate of low-grade gliomas (LGG) has made it difficult to investigate NGF effects on these tumors in preclinical models. In fact, patient-derived low-grade human astrocytoma cells duplicate only a limited number of times in culture before undergoing senescence. Nevertheless, replicative senescence can be counteracted by overexpression of hTERT, the catalytic subunit of telomerase, which potentially increases the proliferative potential of human cells without inducing cancer-associated changes. We have extended, by hTERT transduction, the proliferative potential of a human LGG cell line derived from a pediatric pilocytic astrocytoma (PA) surgical sample. Remarkably, the hTERT-transduced LGG cells showed a behavior similar to that of the parental line in terms of biological responses to NGF treatment, including molecular events associated with induction of NGF-related differentiation. Therefore, transduction of LGG cells with hTERT can provide a valid approach to increase the life-span of patient-derived astrocytoma primary cultures, characterized by a finite proliferative potential.
ISSN:1532-2807
1219-4956
1532-2807
DOI:10.3389/pore.2021.612375