Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027, China.
Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230027, China.
EBioMedicine. 2019 Aug;46:119-132. doi: 10.1016/j.ebiom.2019.07.058. Epub 2019 Jul 30.
Patients undergoing surgical resection of hepatocellular carcinoma (HCC) are at risk of recurrence; however, the underlying mechanism remains poorly understood.
Through the analysis of gene expression profiles in tumour and matched normal tissues from patients with hepatocellular carcinoma (HCC), we identified differences in interleukin-11 (IL-11) expression. Further, we used genetic mouse, orthotopic tumour, chemically induced, and orthotopic allograft models to study the correlation between IL-11 and postsurgical recurrence. Additionally, we conducted a series of experiments, including histology and immunohistochemistry analysis, three-dimensional culture, immunofluorescence, western blotting, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to investigate the role of IL-11-signal transducer and activator of transcription 3 (STAT3) signaling in HCC recurrence.
We demonstrate that IL-11 levels increase after surgery, triggering HCC outgrowth. Accordingly, pharmacological blocking of IL-11-STAT3 signaling in model systems significantly alleviates tumour cell proliferation and suppresses postsurgical recurrence of HCC tumours.
These data demonstrate that IL-11 has a central role in postsurgical HCC recurrence, and that inhibition of IL-11-STAT3 signaling is a potential therapeutic strategy to prevent recurrence. FUND: Natural Science Foundation of China.
接受肝细胞癌 (HCC) 手术切除的患者有复发的风险；然而，其潜在机制仍知之甚少。
通过分析肝细胞癌 (HCC) 患者肿瘤和匹配正常组织的基因表达谱，我们确定了白细胞介素-11 (IL-11) 表达的差异。此外，我们使用遗传小鼠、原位肿瘤、化学诱导和原位同种异体移植模型来研究 IL-11 与术后复发之间的相关性。此外，我们进行了一系列实验，包括组织学和免疫组织化学分析、三维培养、免疫荧光、蛋白质印迹、酶联免疫吸附试验 (ELISA) 和流式细胞术，以研究 IL-11-信号转导和转录激活因子 3 (STAT3) 信号在 HCC 复发中的作用。
我们证明，IL-11 水平在手术后升高，引发 HCC 生长。因此，在模型系统中，通过药理学阻断 IL-11-STAT3 信号可显著抑制肿瘤细胞增殖并抑制 HCC 肿瘤的术后复发。
这些数据表明，IL-11 在手术后 HCC 复发中起核心作用，抑制 IL-11-STAT3 信号是预防复发的潜在治疗策略。
国家自然科学基金。
