Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
Int J Oncol. 2020 Dec;57(6):1293-1306. doi: 10.3892/ijo.2020.5134. Epub 2020 Oct 15.
Accumulating evidence suggests that inflammation is present in solid tumors. However, it is poorly understood whether inflammation exists in glioma and how it affects the metabolic signature of glioma. By analyzing immunohistochemical data and gene expression data downloaded from bioinformatic datasets, the present study revealed an accumulation of inflammatory cells in glioma, activation of microglia, upregulation of proinflammatory factors (including IL‑6, IL‑8, hypoxia‑inducible factor‑1α, STAT3, NF‑κB1 and NF‑κB2), destruction of mitochondrial structure and altered expression levels of electron transfer chain complexes and metabolic enzymes. By monitoring glioma cells following proinflammatory stimulation, the current study observed a remodeling of their mitochondrial network via mitochondrial fission. More than half of the mitochondria presented ring‑shaped or spherical morphologies. Transmission electron microscopic analyses revealed mitochondrial swelling with partial or total cristolysis. Furthermore, proinflammatory stimuli resulted in increased generation of reactive oxygen species, decreased mitochondrial membrane potential and reprogrammed metabolism. The defective mitochondria were not eliminated via mitophagy. However, cell viability was not affected, and apoptosis was decreased in glioma cells after proinflammatory stimuli. Overall, the present findings suggested that inflammation may be present in glioma and that glioma cells may be resistant to inflammation‑induced mitochondrial dysfunction.
越来越多的证据表明炎症存在于实体肿瘤中。然而,人们对胶质瘤中是否存在炎症以及炎症如何影响胶质瘤的代谢特征知之甚少。本研究通过分析从生物信息数据集下载的免疫组织化学数据和基因表达数据,揭示了胶质瘤中炎症细胞的积累、小胶质细胞的激活、促炎因子(包括 IL-6、IL-8、缺氧诱导因子-1α、STAT3、NF-κB1 和 NF-κB2)的上调、线粒体结构的破坏以及电子传递链复合物和代谢酶表达水平的改变。通过监测促炎刺激后的胶质瘤细胞,本研究观察到它们的线粒体网络通过线粒体裂变进行重塑。超过一半的线粒体呈现出环形或球形形态。透射电子显微镜分析显示线粒体肿胀伴部分或完全嵴溶解。此外,促炎刺激导致活性氧生成增加、线粒体膜电位降低和代谢重新编程。缺陷线粒体不会通过线粒体自噬消除。然而,在促炎刺激后,胶质瘤细胞的细胞活力未受影响,细胞凋亡减少。总体而言,这些发现表明炎症可能存在于胶质瘤中,并且胶质瘤细胞可能对炎症诱导的线粒体功能障碍具有抗性。