Runge Josephine, Garbers Christoph, Lokau Juliane
Institute of Pathology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Institute of Clinical Biochemistry, Hannover Medical School (MHH), Hannover, Germany.
Contemp Oncol (Pozn). 2024;28(2):105-113. doi: 10.5114/wo.2024.142211. Epub 2024 Aug 15.
The cytokine interleukin-11 (IL-11) binds on its target cells to a membrane-bound IL-11R, which results in homodimerization of the signal-transducing β-receptor gp130. Recent studies have uncovered a pro- inflammatory role in several diseases, including different tumor entities, and mouse models have revealed a crucial role of the IL-11/IL-11R axis in gastric cancer. However, studies regarding human gastric cancer are sparse, and whether the results obtained in mouse models also hold true in the human situation is little investigated.
We analyzed gene expression of and in different gastric tumor and immune cell lines. Furthermore, we stimulated these cell lines with exogenous cytokines and determined intracellular signaling. Finally, we analyzed gene expression data of gastric tumor patients and correlated them with overall patient survival.
This study showed that different gastric tumor cell lines respond to IL-6 classic and trans-signaling, but only slightly to stimulation with IL-11. We observed that monocyte-like cell lines expressed high levels of IL-6R and responded to IL-6, but not to stimulation with IL-11. Using gene expression data, we found that and are not overexpressed in human gastric cancer tissue and do not correlate with patient survival. However, low expression is associated with higher overall survival.
We provided evidence for IL-6 but not IL-11 signaling in gastric tumor cells and demonstrated that expression in gastric tumors is associated with overall survival of patients.
细胞因子白细胞介素-11(IL-11)在其靶细胞上与膜结合的IL-11受体结合,这导致信号转导β受体gp130的同二聚化。最近的研究发现IL-11在包括不同肿瘤实体在内的几种疾病中具有促炎作用,并且小鼠模型揭示了IL-11/IL-11受体轴在胃癌中的关键作用。然而,关于人类胃癌的研究很少,并且在小鼠模型中获得的结果在人类情况下是否也成立鲜有研究。
我们分析了不同胃肿瘤和免疫细胞系中[具体基因名称未给出]和[具体基因名称未给出]的基因表达。此外,我们用外源性细胞因子刺激这些细胞系并确定细胞内信号传导。最后,我们分析了胃肿瘤患者的基因表达数据并将其与患者总体生存率相关联。
本研究表明,不同的胃肿瘤细胞系对IL-6经典信号传导和转信号传导有反应,但对IL-11刺激的反应较弱。我们观察到单核细胞样细胞系表达高水平的IL-6受体并对IL-6有反应,但对IL-11刺激无反应。利用基因表达数据,我们发现[具体基因名称未给出]和[具体基因名称未给出]在人类胃癌组织中未过度表达,且与患者生存率无关。然而,[具体基因名称未给出]低表达与较高的总体生存率相关。
我们为胃肿瘤细胞中的IL-6而非IL-11信号传导提供了证据,并证明胃肿瘤中[具体基因名称未给出]的表达与患者的总体生存率相关。