研究动态
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嗜酸性粒细胞通过GM-CSF和半胱氨酸-白三烯诱导胶质母细胞瘤细胞的抑制和细胞凋亡。

Eosinophils induces glioblastoma cell suppression and apoptosis - Roles of GM-CSF and cysteinyl-leukotrienes.

发表日期:2023 Aug 01
作者: Bruno Marques Vieira, Vitória Santório de São José, Paulo Soares Niemeyer Filho, Vivaldo Moura-Neto
来源: INTERNATIONAL IMMUNOPHARMACOLOGY

摘要:

胶质母细胞瘤是成年人最常见和致命的原发性脑肿瘤。尽管目前存在癌症治疗方法,但肿瘤复发率高、生存率低。需要新的抗肿瘤治疗方法。嗜酸性粒细胞在过敏性疾病中非常突出,并在多种人类脑肿瘤中积聚。最近,嗜酸性粒细胞的抗肿瘤作用已成为研究的目标,因为嗜酸性粒细胞释放多种细胞毒性因子,可导致细胞损害和死亡。本研究旨在评估嗜酸性粒细胞与胶质母细胞瘤细胞的相互作用、嗜酸性粒细胞可能杀死胶质母细胞瘤细胞的机制,以及过敏/哮喘如何影响胶质母细胞瘤的预后。使用哮喘和非哮喘捐赠者的嗜酸性粒细胞和血清与不同的胶质母细胞瘤细胞系进行培养。胶质母细胞瘤细胞通过GM-CSF信号诱导嗜酸性粒细胞的招募,并在GM-CSF依赖性的方式下激活和增加嗜酸性粒细胞的生存能力和功能。嗜酸性粒细胞通过Fas/FasL减少胶质母细胞瘤细胞的新陈代谢、增殖和迁移。半胱氨酸类白三烯对胶质母细胞瘤细胞迁移和增殖具有促进作用。半胱氨酸类白三烯能够增加胶质母细胞瘤细胞的增殖和迁移,并激活抑制胶质母细胞瘤的嗜酸性粒细胞。嗜酸性粒细胞有潜力成为胶质母细胞瘤治疗中的关键细胞,因为过敏和嗜酸性粒细胞增多与胶质母细胞瘤预后良好相关。嗜酸性粒细胞被激活并附着在胶质母细胞瘤细胞上,通过其细胞毒性功能,通过Fas/FasL抑制胶质母细胞瘤细胞的新陈代谢、增殖、迁移,并诱导细胞死亡。 版权所有 ©2023 Elsevier B.V. All rights reserved.
Glioblastoma is the most common and lethal primary brain tumor in adults. Despite the available cancer treatments, the recurrence of the tumor is high, and the survival rate is low. New approaches to antitumor therapies are needed. Eosinophils are prominent in allergic diseases and accumulate in several human brain tumors. Recently, the antitumor role of eosinophils has been targeted as eosinophils release several cytotoxic factors that induce cell impairment and death.Here we aim to evaluate the interaction of the eosinophil and glioblastoma cells, the mechanism involved in the potential killing of the glioblastoma cells by the eosinophils, and how allergy/asthma could confer a better glioblastoma prognosis.Eosinophils and serum from asthmatic and non-asthmatic donors were cultivated with different glioblastoma cell lines.Glioblastoma cells recruit eosinophils via GM-CSF signaling, activating and increasing eosinophil survivability and function on a GM-CSF-dependent manner. Eosinophils reduce glioblastoma cells metabolism, proliferation, and migration, via Fas/FasL. Cysteinyl-leukotrienes are accounted for the asthmatic serum enhancement of the glioblastoma cell migration and proliferation. Cysteinyl-leukotrienes enhance glioblastoma cell proliferation and migration, albeit activate eosinophils that suppress glioblastoma cells.Eosinophils have the potential to be key cells on glioblastoma therapeutics, as allergy and eosinophilia are correlated with a better glioblastoma prognosis. Eosinophils are elicited and attach to glioblastoma cells, where, by its cytotoxic function, via Fas/FasL, hind glioblastoma cell metabolism, proliferation, migration, and induce cell death.Copyright © 2023 Elsevier B.V. All rights reserved.