Pan Yanyun, Qiu Yuangang, Zhou Xinbin, Mao Wei, Xu Xiaoming
Department of Cardiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
Department of Cardiology, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory of Integrative Chinese and Western Medicine for Diagnosis and Treatment of Circulatory Diseases, Hangzhou, China.
Front Oncol. 2025 Apr 3;15:1454546. doi: 10.3389/fonc.2025.1454546. eCollection 2025.
Cancer-associated fibroblasts (CAFs), the most abundant stromal cells in the tumor microenvironment (TME), control tumor growth through production and organization of the extracellular matrix (ECM) for a long time. However, the results from different studies that have focused on targeting CAFs to disturb tumor progression are extremely controversial. Recent studies using advanced single-cell RNA sequencing technology (scRNAseq) combined with multiple genetically engineered mouse models have identified diverse CAF subpopulations in the premalignant liver microenvironment (PME) of hepatocellular carcinoma (HCC) and TME of intrahepatic cholangiocarcinoma (ICC), providing a deeper understanding of the exact roles of each CAF subpopulation in cancer development. This review focuses on the specific protein markers, signaling pathways, and functions of various emerging CAF subclusters that contribute to the development of ICC and HCC. Elucidating the role and regulation of CAF subpopulations under different pathophysiological conditions will facilitate the discovery of new therapeutics that modulate CAF activity.
癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）中最丰富的基质细胞，长期以来通过细胞外基质（ECM）的产生和组织来控制肿瘤生长。然而，不同研究中针对CAFs以干扰肿瘤进展的结果极具争议。最近使用先进的单细胞RNA测序技术（scRNAseq）结合多种基因工程小鼠模型的研究，已经在肝细胞癌（HCC）的癌前肝脏微环境（PME）和肝内胆管癌（ICC）的TME中鉴定出不同的CAF亚群，从而更深入地了解每个CAF亚群在癌症发展中的确切作用。这篇综述聚焦于各种新兴CAF亚群的特定蛋白质标志物、信号通路和功能，这些亚群有助于ICC和HCC的发展。阐明不同病理生理条件下CAF亚群的作用和调控，将有助于发现调节CAF活性的新疗法。
