Papadakos Stavros P, Arvanitakis Konstantinos, Stergiou Ioanna E, Vallilas Christos, Sougioultzis Stavros, Germanidis Georgios, Theocharis Stamatios
First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 10679 Athens, Greece.
First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
Pharmaceutics. 2023 Oct 13;15(10):2460. doi: 10.3390/pharmaceutics15102460.
Hepatocellular carcinoma (HCC) stands as a significant contributor to global cancer-related mortality. Chronic inflammation, often arising from diverse sources such as viral hepatitis, alcohol misuse, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH), profoundly influences HCC development. Within this context, the interplay of extracellular vesicles (EVs) gains prominence. EVs, encompassing exosomes and microvesicles, mediate cell-to-cell communication and cargo transfer, impacting various biological processes, including inflammation and cancer progression. Toll-like receptor 4 (TLR4), a key sentinel of the innate immune system, recognizes both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), thereby triggering diverse signaling cascades and pro-inflammatory cytokine release. The intricate involvement of the TLR4 signaling pathway in chronic liver disease and HCC pathogenesis is discussed in this study. Moreover, we delve into the therapeutic potential of modulating the TLR4 pathway using EVs as novel therapeutic agents for HCC. This review underscores the multifaceted role of EVs in the context of HCC and proposes innovative avenues for targeted interventions against this formidable disease.
肝细胞癌（HCC）是全球癌症相关死亡率的一个重要因素。慢性炎症通常源于多种因素，如病毒性肝炎、酒精滥用、非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH），对HCC的发展有深远影响。在此背景下，细胞外囊泡（EVs）的相互作用变得突出。EVs包括外泌体和微囊泡，介导细胞间通讯和货物转运，影响包括炎症和癌症进展在内的各种生物学过程。Toll样受体4（TLR4）是先天免疫系统的关键哨兵，可识别病原体相关分子模式（PAMPs）和损伤相关分子模式（DAMPs），从而触发各种信号级联反应和促炎细胞因子释放。本研究讨论了TLR4信号通路在慢性肝病和HCC发病机制中的复杂参与情况。此外，我们深入探讨了使用EVs作为HCC新型治疗药物调节TLR4通路的治疗潜力。这篇综述强调了EVs在HCC背景下的多方面作用，并提出了针对这种严重疾病的靶向干预创新途径。
