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冯唐, 杨欣蕊, 王琦为, 等. 肝癌外泌体在肿瘤微环境细胞间通讯中的作用[J]. 四川大学学报(医学版), 2024, 55(1): 6-12. DOI: 10.12182/20240160203
引用本文: 冯唐, 杨欣蕊, 王琦为, 等. 肝癌外泌体在肿瘤微环境细胞间通讯中的作用[J]. 四川大学学报(医学版), 2024, 55(1): 6-12. DOI: 10.12182/20240160203
FENG Tang, YANG Xinrui, WANG Qiwei, et al. Hepatocellular Carcinoma-Derived Exosomes: Key Players in Intercellular Communication Within the Tumor Microenvironment[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(1): 6-12. DOI: 10.12182/20240160203
Citation: FENG Tang, YANG Xinrui, WANG Qiwei, et al. Hepatocellular Carcinoma-Derived Exosomes: Key Players in Intercellular Communication Within the Tumor Microenvironment[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(1): 6-12. DOI: 10.12182/20240160203

肝癌外泌体在肿瘤微环境细胞间通讯中的作用

Hepatocellular Carcinoma-Derived Exosomes: Key Players in Intercellular Communication Within the Tumor Microenvironment

  • 摘要: 肝细胞肝癌(hepatocellular carcinoma, HCC)是世界上最致命的癌症之一。由于HCC发病隐匿、进展迅速且缺乏有效的治疗方法,预后极差,其5年平均生存率低于10%。肿瘤微环境是HCC发生发展所处的内环境,可调节HCC的起源、发展、侵袭和转移。肝癌细胞在癌症进展过程中可以通过释放含有特异信号的外泌体调控肿瘤微环境中的肿瘤细胞、癌相关成纤维细胞、癌相关免疫细胞等不同细胞的生物学行为,进而促进癌症进展。然而,外泌体在这些过程中对具体细胞调控的确切分子机制和作用仍不清楚。本综述首先介绍了HCC微环境的组成和肿瘤微环境中外泌体的来源和特征以及力学因素对外泌体的影响。其次,本综述重点讨论了HCC外泌体对微环境中不同类型细胞的作用。我们看到,在包括肝癌在内的临床癌症治疗中使用外泌体作为载体仍然有许多必须克服的困难。首先,外泌体的同质性很难得到保证。其次,外泌体主要通过皮下注射给药,虽然这种方法简单易行,但吸收效率并不理想。第三,外泌体提取方法有限且效率低,因此难以大量制备外泌体。特别是对于外泌体介导的肿瘤免疫治疗,确保使用的外泌体数量足以引发有效的肿瘤免疫反应非常重要。随着鉴定、分离和纯化技术的改进,外泌体有望成功运用于早期HCC的临床诊断和肝癌的临床治疗中。

     

    Abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Due to the insidious onset and rapid progression and a lack of effective treatments, the prognosis of patients with HCC is extremely poor, with the average 5-year survival rate being less than 10%. The tumor microenvironment (TME), the internal environment in which HCC develops, can regulate the oncogenesis, development, invasion, and metastasis of HCC. During the process of cancer progression, HCC cells can regulate the biological behaviors of tumor cells, cancer-associated fibroblasts, cancer-associated immune cells, and other cells in the TME by releasing exosomes containing specific signals, thereby promoting cancer progression. However, the exact molecular mechanisms and the roles of exosomes in the specific cellular regulation of these processes are not fully understood. Herein, we summarized the TME components of HCC, the sources and the biological traits of exosomes in the TME, and the impact of mechanical factors on exosomes. In addition, special attention was given to the discussion of the effects of HCC-exosomes on different types of cells in the microenvironment. There are still many difficulties to be overcome before exosomes can be applied as carriers in clinical cancer treatment. First of all, the homogeneity of exosomes is difficult to ensure. Secondly, exosomes are mainly administered through subcutaneous injection. Although this method is simple and easy to implement, the absorption efficiency is not ideal. Thirdly, exosome extraction methods are limited in number and inefficient, making it difficult to prepare exosomes in large quantities. It is important to ensure that exosomes are used in sufficient quantities to trigger an effective tumor immune response, especially for exosome-mediated tumor immunotherapy. With the improvement in identification, isolation, and purification technology, exosomes are expected to be successfully used in the clinical diagnosis of early-stage HCC and the clinical treatment of liver cancer.

     

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