Department of General, Visceral, Tumor and Transplantation Surgery, University Hospital of Cologne, Kerpener Straße 62, 50937 Cologne, Germany.
Institute of Pathology, University Hospital of Cologne, Kerpener Straße 62, 50937 Cologne, Germany.
Int J Mol Sci. 2020 Mar 23;21(6):2215. doi: 10.3390/ijms21062215.
(1) Background: IL-17A accelerates pancreatic intraepithelial neoplasia (PanIN) progression. In this study, we examined whether IL-17A/IL-17RA promotes pancreatic ductal adenocarcinoma (PDAC) aggressiveness in terms of survival and cancer stem cell modulation. (2) Methods: In vitro, the wound-healing assay, the sphere formation assay, and flow cytometry were applied to assess cancer stem cell features. In vivo, pancreatic tumors were induced in C57BL/6 mice using electroporation with oncogenic plasmids (P53-/- R172H; KrasG12V). Anti-IL-17 antibodies were administered as immunotherapy. We analyzed IL-17A/IL-17RA related survival using publicly available transcriptomic data ( = 903). (3) Results: IL-17A/IL-17RA expression was not related to survival in PDAC patients. IL-17A neither induces stem cell markers nor increases sphere formation and cell motility in vitro. Blocking the IL-17A/IL-17RA axis in a murine pancreatic cancer model did not improve the survival of mice, but reduced the tumor burden slightly. (4) Conclusions: IL-17A does not promote stem cell expansion in PDAC cell lines. Blocking IL-17A/IL-17RA signaling does not interfere with pancreatic cancer development and progression and may not be considered as a promising monotherapy for PDAC.
(1) 背景:IL-17A 加速胰腺上皮内瘤变(PanIN)进展。在这项研究中,我们研究了 IL-17A/IL-17RA 是否通过调节癌症干细胞来促进胰腺导管腺癌(PDAC)的侵袭性。(2) 方法:在体外,我们应用划痕愈合试验、球体形成试验和流式细胞术来评估癌症干细胞特征。在体内,使用电穿孔将致癌质粒(P53-/- R172H;KrasG12V)导入 C57BL/6 小鼠中以诱导胰腺肿瘤。使用抗 IL-17 抗体进行免疫治疗。我们分析了公共转录组数据(=903)中与 IL-17A/IL-17RA 相关的生存情况。(3) 结果:IL-17A/IL-17RA 的表达与 PDAC 患者的生存无关。IL-17A 既不会诱导干细胞标志物的表达,也不会增加体外球体形成和细胞迁移。在小鼠胰腺癌模型中阻断 IL-17A/IL-17RA 轴并不能改善小鼠的生存,但能轻微降低肿瘤负担。(4) 结论:IL-17A 不会促进 PDAC 细胞系中干细胞的扩增。阻断 IL-17A/IL-17RA 信号不会干扰胰腺癌的发生和进展,因此可能不能作为 PDAC 的一种有前途的单一疗法。