Department of Neurosurgery, Beilun District People's Hospital of Ningbo City, Ningbo, Zhejiang, 315800, China.
Department of Neurosurgery, Beilun District People's Hospital of Ningbo City, Ningbo, Zhejiang, 315800, China.
Pathol Res Pract. 2021 Jul;223:153463. doi: 10.1016/j.prp.2021.153463. Epub 2021 May 5.
The presence and clinical significance of IL-17 and IL-17-expressing cells have been studied for several cancers, although their correlation with tumor development remains controversial. Peripheral blood was collected from healthy donors and glioma patients to isolate peripheral blood mononuclear cells (PBMCs). The percentage of IL-17-expressing cells and the production of inflammatory cytokines in PBMCs and tissues were measured. Human IL‑17 cDNA was then inserted into the pEGFP‑N1 plasmid and transfected into the glioma U87MG cell line, and tumstatin was used to block the effect of the IL-17 overexpression. Stem cell transcription factors were evaluated in each group using qRT-PCR and western blotting, and proliferation and migration were detected using colony formation and wound-healing assays. The cells were then subcutaneously inoculated into nude mice to evaluate the growth of glioma. Compared with healthy donors, the PBMCs from glioma patients showed a significant accumulation of IL-17-expressing T cells. Th17 cell differentiation-related cytokines (IL-23, TGF-β and IL-6) were increased in the tumor microenvironment. IL‑17 transfection increased the mRNA and protein expression of stem cell transcription factors in U87MG cells in vitro. The proliferation and migration of U87MG cells were also increased. Moreover, the pEGFP‑N1‑IL‑17‑U87MG cells grew more rapidly than other cells. However, tumstatin-treated U87MG cells showed significantly inhibited the effects of IL-17 overexpression. Tumstatin effectively suppressed IL-17-derived U87MG cell growth by downregulating stem cell maintenance factors and inducing proliferation and migration. These findings indicated that IL-17 represents a potential prognostic marker for glioma, while tumstatin has potential in the treatment for glioma.
IL-17 和表达 IL-17 的细胞的存在及其临床意义已在多种癌症中得到研究，尽管其与肿瘤发展的相关性仍存在争议。从健康供体和神经胶质瘤患者中采集外周血以分离外周血单核细胞 (PBMC)。测量 PBMC 和组织中表达 IL-17 的细胞的百分比和炎症细胞因子的产生。然后将人 IL-17 cDNA 插入 pEGFP-N1 质粒并转染至神经胶质瘤 U87MG 细胞系，并用 tumstatin 阻断 IL-17 过表达的作用。使用 qRT-PCR 和 Western blot 在每组中评估干细胞转录因子，并用集落形成和划痕愈合测定检测增殖和迁移。然后将细胞皮下接种到裸鼠中以评估神经胶质瘤的生长。与健康供体相比，神经胶质瘤患者的 PBMC 显示出表达 IL-17 的 T 细胞明显积聚。肿瘤微环境中 Th17 细胞分化相关细胞因子（IL-23、TGF-β 和 IL-6）增加。IL-17 转染增加了体外 U87MG 细胞中干细胞转录因子的 mRNA 和蛋白表达。U87MG 细胞的增殖和迁移也增加了。此外，pEGFP-N1-IL-17-U87MG 细胞比其他细胞生长得更快。然而，用 tumstatin 处理的 U87MG 细胞显示出明显抑制了 IL-17 过表达的作用。Tumstatin 通过下调干细胞维持因子并诱导增殖和迁移，有效抑制了 IL-17 衍生的 U87MG 细胞的生长。这些发现表明 IL-17 代表神经胶质瘤的一个潜在预后标志物，而 tumstatin 具有神经胶质瘤治疗的潜力。
