Lopes Marta, Vieira de Castro Joana, Pojo Marta, Gonçalves Céline S, Martins Eduarda P, Coimbra Bárbara, Sotiropoulos Ioannis, Sousa Nuno, Rodrigues Ana João, Costa Bruno M
Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Front Oncol. 2022 Mar 25;12:856210. doi: 10.3389/fonc.2022.856210. eCollection 2022.
The existence of a clear association between stress and cancer is still a matter of debate. Recent studies suggest that chronic stress is associated with some cancer types and may influence tumor initiation and patient prognosis, but its role in brain tumors is not known. Glioblastoma (GBM) is a highly malignant primary brain cancer, for which effective treatments do not exist. Understanding how chronic stress, or its effector hormones glucocorticoids (GCs), may modulate GBM aggressiveness is of great importance. To address this, we used both syngeneic and xenograft orthotopic mouse models of GBM, in immunocompetent C57BL/6J or immunodeficient NSG mice, respectively, to evaluate how different paradigms of stress exposure could influence GBM aggressiveness and animals' overall survival (OS). Our results demonstrated that a previous exposure to exogenous corticosterone administration, chronic restraint stress, or chronic unpredictable stress do not impact the OS of these mice models of GBM. Concordantly, analyses of various GBM-relevant genes showed similar intra-tumor expression levels across all experimental groups. These findings suggest that corticosterone and chronic stress do not significantly affect GBM aggressiveness in murine models.
压力与癌症之间是否存在明确关联仍是一个有争议的问题。最近的研究表明,慢性压力与某些癌症类型有关,可能会影响肿瘤的发生和患者预后,但其在脑肿瘤中的作用尚不清楚。胶质母细胞瘤(GBM)是一种高度恶性的原发性脑癌,目前尚无有效的治疗方法。了解慢性压力或其效应激素糖皮质激素(GCs)如何调节GBM的侵袭性非常重要。为了解决这个问题,我们分别在免疫健全的C57BL/6J小鼠或免疫缺陷的NSG小鼠中使用了GBM的同基因和异种移植原位小鼠模型,以评估不同的应激暴露模式如何影响GBM的侵袭性和动物的总生存期(OS)。我们的结果表明,先前给予外源性皮质酮、慢性束缚应激或慢性不可预测应激不会影响这些GBM小鼠模型的OS。一致地,对各种与GBM相关基因的分析显示,所有实验组的肿瘤内表达水平相似。这些发现表明,皮质酮和慢性应激不会显著影响小鼠模型中GBM的侵袭性。