Mao Ping, Wang Tuo, Du Chang-Wang, Yu Xiao, Wang Mao-De
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Mol Biol Rep. 2023 Oct;50(10):8015-8023. doi: 10.1007/s11033-023-08671-3. Epub 2023 Aug 4.
The tumor microenvironment contains chemokines that play a crucial role in various processes, such as tumorigenesis, inflammation, and therapy resistance, in different types of cancer. CXCL5 is a significant chemokine that has been shown to promote tumor proliferation, invasion, angiogenesis, and therapy resistance when overexpressed in various types of cancer. This research aims to investigate the impact of CXCL5 on the biological functions of glioblastoma (GBM).
The TCGA GBM and GEO databases were utilized to perform transcriptome microarray analysis and oncogenic signaling pathway analysis of CXCL5 in GBM. Validation of CXCL5 expression was performed using RT-qPCR and Western Blot. The impact of CXCL5 on cell proliferation, tumorigenesis, and angiogenesis in GBM was assessed through various methods, including cell proliferation assay, cloning assay, intracranial xenograft tumor models, and tube formation assay. Clinical prognosis was evaluated in 59 samples of gliomas with varying degrees of malignancy (grades 2, 3, and 4) and the TCGA GBM database, based on CXCL5 expression levels. The activities of the JAK-STAT and NF-κB signaling pathways were detected using Western Blot.
The expression of CXCL5 was highly enriched in GBM. Moreover, the inhibition of CXCL5 showed a significant efficacy in suppressing cellular proliferation and angiogenesis, resulting in extended survival rates in xenograft mouse models in comparison to the control group. Notably, pretreatment with dapsone exhibited a reversal of the impact of CXCL5 on the formation of colonies and tubes in GBM cells. Elevated expression of CXCL5 was correlated with poor outcomes in GBM patients. Furthermore, the overexpression of CXCL5 has been associated with the activation of JAK-STAT and NF-κB signaling pathways.
CXCL5 plays an important role in tumorigenesis and angiogenesis, indicating the potential for novel therapies targeting CXCL5 in GBM.
肿瘤微环境包含趋化因子，其在不同类型癌症的多种过程中发挥关键作用，如肿瘤发生、炎症和治疗抗性。CXCL5是一种重要的趋化因子，已表明在多种类型癌症中过表达时可促进肿瘤增殖、侵袭、血管生成和治疗抗性。本研究旨在探讨CXCL5对胶质母细胞瘤（GBM）生物学功能的影响。
利用TCGA GBM和GEO数据库对GBM中CXCL5进行转录组微阵列分析和致癌信号通路分析。使用RT-qPCR和蛋白质免疫印迹法验证CXCL5的表达。通过多种方法评估CXCL5对GBM细胞增殖、肿瘤发生和血管生成的影响，包括细胞增殖试验、克隆试验、颅内异种移植肿瘤模型和管形成试验。基于CXCL5表达水平，在59例不同恶性程度（2级、3级和4级）的胶质瘤样本和TCGA GBM数据库中评估临床预后。使用蛋白质免疫印迹法检测JAK-STAT和NF-κB信号通路的活性。
CXCL5的表达在GBM中高度富集。此外，抑制CXCL5在抑制细胞增殖和血管生成方面显示出显著效果，与对照组相比，异种移植小鼠模型的存活率延长。值得注意的是，用氨苯砜预处理可逆转CXCL5对GBM细胞中集落和管形成的影响。CXCL5表达升高与GBM患者的不良预后相关。此外，CXCL5的过表达与JAK-STAT和NF-κB信号通路的激活有关。
CXCL5在肿瘤发生和血管生成中起重要作用，表明针对GBM中CXCL5的新型疗法具有潜力。
