Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Institute of Internal Medicine, Periodic Fever and Rare Diseases Center, Fondazione Policlinico A. Gemelli, IRCCS, Rome, Italy.
Pathol Oncol Res. 2021 Apr 2;27:612375. doi: 10.3389/pore.2021.612375. eCollection 2021.
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.
神经生长因子（NGF）是一种神经营养因子，可调节人神经胶质瘤的生长，并通过与原肌球蛋白受体激酶 A（TrkA）受体结合诱导细胞分化，尽管其在控制神经胶质瘤存活中的作用存在争议。不幸的是，低级神经胶质瘤（LGG）的生长缓慢，使得难以在临床前模型中研究 NGF 对这些肿瘤的作用。事实上，患者来源的低级别人星形细胞瘤细胞在培养中仅复制有限的次数，然后就会衰老。然而，端粒酶催化亚基 hTERT 的过表达可以逆转复制性衰老，这可能会增加人细胞的增殖潜力，而不会引起与癌症相关的变化。我们通过 hTERT 转导，延长了源自儿科毛细胞星形细胞瘤（PA）手术样本的人 LGG 细胞系的增殖潜力。值得注意的是，hTERT 转导的 LGG 细胞在对 NGF 处理的生物学反应方面表现出与亲本系相似的行为，包括与诱导 NGF 相关分化相关的分子事件。因此，hTERT 转导 LGG 细胞可以为增加具有有限增殖潜力的患者来源星形细胞瘤原代培养物的寿命提供有效方法。
