Cui Guanghua, Liu Wei, Sun Xiaoke, Bai Yun, Ding Meijuan, Zhao Ning, Guo Jialu, Qu Di, Wang Song, Qin Luyao, Yang Yu
Department of Oncology, the Second Affiliated Hospital of Harbin Medical University, 150081 Harbin, Heilongjiang, China.
Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin 150086, China.
Int J Biol Macromol. 2025 Jan;287:138523. doi: 10.1016/j.ijbiomac.2024.138523. Epub 2024 Dec 7.
Hepatocellular carcinoma (HCC) represents a particularly aggressive form of cancer, characterized by its rapid progression and a complex interplay with the surrounding immune cellular environment. The primary objective of this study was to comprehensively investigate the role of ANGPTL4 in the context of HCC, utilizing RNA sequencing (RNA-seq) techniques to explore its impact on the M2 polarization of tumor-associated macrophages (TAM) and to uncover potential mechanisms driving HCC progression. To achieve this, we performed a transcriptome analysis of HCC cell lines, alongside cells obtained after co-culturing these lines with macrophages. By comparing gene expression profiles between the experimental groups exposed to ANGPTL4 and control groups, we aimed to identify specific molecular pathways associated with ANGPTL4's function. In addition to gene expression analysis, we employed flow cytometry to assess the polarization status of TAM. Furthermore, we utilized immunohistochemistry to evaluate the distribution of macrophages within HCC tissues and to quantify the expression levels of M2 macrophage markers. The results derived from RNA-seq analysis were particularly revealing; treatment with ANGPTL4 led to a significant upregulation of genes linked to M2 polarization, notably including CD206 and Arg1. In subsequent experimental observations, it became evident that ANGPTL4 not only facilitated the M2 polarization of macrophages but also enhanced the proliferation and migratory capacity of HCC cells through the upregulation of these same cytokines.
肝细胞癌（HCC）是一种侵袭性特别强的癌症形式，其特点是进展迅速，且与周围免疫细胞环境存在复杂的相互作用。本研究的主要目的是全面探究血管生成素样蛋白4（ANGPTL4）在HCC背景下的作用，利用RNA测序（RNA-seq）技术来探索其对肿瘤相关巨噬细胞（TAM）的M2极化的影响，并揭示驱动HCC进展的潜在机制。为实现这一目标，我们对HCC细胞系以及将这些细胞系与巨噬细胞共培养后获得的细胞进行了转录组分析。通过比较暴露于ANGPTL4的实验组和对照组之间的基因表达谱，我们旨在确定与ANGPTL4功能相关的特定分子途径。除了基因表达分析，我们还采用流式细胞术评估TAM的极化状态。此外，我们利用免疫组织化学来评估巨噬细胞在HCC组织中的分布，并量化M2巨噬细胞标志物的表达水平。RNA-seq分析得出的结果特别有启发性；用ANGPTL4处理导致与M2极化相关的基因显著上调，尤其包括CD206和精氨酸酶1（Arg1）。在随后的实验观察中，很明显ANGPTL4不仅促进了巨噬细胞的M2极化，还通过上调相同的细胞因子增强了HCC细胞的增殖和迁移能力。
