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

FENG Tang, YANG Xinrui, WANG Qiwei, LIU Xiaoheng

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.


Keywords: Exosomes,  Tumor microenvironment,  Hepatocellular carcinoma, Intercellular communication, Review


Full Text:

PDF


References


QI J， LI M， WANG L， et al. National and subnational trends in cancer burden in China, 2005-20: an analysis of national mortality surveillance data. Lancet Public Health，2023，8(12): e943–e955. doi: 10.1016/S2468-2667(23)00211-6.

CHEN X， KOU L， XIE X， et al. Prognostic biomarkers associated with immune checkpoint inhibitors in hepatocellular carcinoma. Immunology，2024. doi: 10.1111/imm.13751.

MINAMI Y， NISHIDA N， KUDO M. Imaging diagnosis of various hepatocellular carcinoma subtypes and its hypervascular mimics: differential diagnosis based on conventional interpretation and artificial intelligence. Liver Cancer，2023，12(2): 103–115. doi: 10.1159/000528538.

GALLAGE S， GARCIA-BECCARIA M， SZYDLOWSKA M， et al. The therapeutic landscape of hepatocellular carcinoma. Med，2021，2(5): 505–552. doi: 10.1016/j.medj.2021.03.002.

WEI Q， TAN N， XIONG S， et al. Deep learning methods in medical image-based hepatocellular carcinoma diagnosis: a systematic review and meta-analysis. Cancers (Basel)，2023，15(23): 5701. doi: 10.3390/cancers15235701.

LI Z， ZHANG Z， FANG L， et al. Tumor microenvironment composition and related therapy in hepatocellular carcinoma. J Hepatocell Carcinoma，2023，10: 2083–2099. doi: 10.2147/JHC.S436962.

MIELGO A， SCHMID M C. Liver tropism in cancer: the hepatic metastatic niche. Cold Spring Harb Perspect Med，2020，10(3): a037259. doi: 10.1101/cshperspect.a037259.

LIU M， LAI Z， YUAN X， et al. Role of exosomes in the development, diagnosis, prognosis and treatment of hepatocellular carcinoma. Mol Med，2023，29(1): 136. doi: 10.1186/s10020-023-00731-5.

ZHOU X， JIA Y， MAO C， et al. Small extracellular vesicles: non-negligible vesicles in tumor progression, diagnosis, and therapy. Cancer Lett，2024，580: 216481. doi: 10.1016/j.canlet.2023.216481.

LI Y， JIN G， LIU N， et al. The post-chemotherapy changes of tumor physical microenvironment: targeting extracellular matrix to address chemoresistance. Cancer Lett，2024，582: 216583. doi: 10.1016/j.canlet. 2023.216583.

MONTERAN L， ZAIT Y， EREZ N. It's all about the base: stromal cells are central orchestrators of metastasis. Trends Cancer，2023: S2405-8033(23)00235-2. doi: 10.1016/j.trecan.2023.11.004.

GUO X， CHEN M， CAO L， et al. Cancer-associated fibroblasts promote migration and invasion of non-small cell lung cancer cells via mir-101-3p mediated VEGFA secretion and AKT/eNOS pathway. Front Cell Dev Biol，2021，9: 764151. doi: 10.3389/fcell.2021.764151.

PENG L， WANG D， HAN Y， et al. Emerging role of cancer-associated fibroblasts-derived exosomes in tumorigenesis. Front Immunol，2021，12: 795372. doi: 10.3389/fimmu.2021.795372.

JIA W， LIANG S， CHENG B， et al. The role of cancer-associated fibroblasts in hepatocellular carcinoma and the value of traditional chinese medicine treatment. Front Oncol，2021，11: 763519. doi: 10.3389/fonc.2021.763519.

KOYAMA Y， BRENNER D A. Liver inflammation and fibrosis. J Clin Invest，2017，127(1): 55–64. doi: 10.1172/JCI88881.

BAGLIERI J， BRENNER D A， KISSELEVA T. The role of fibrosis and liver-associated fibroblasts in the pathogenesis of hepatocellular carcinoma. Int J Mol Sci，2019，20(7): 1723. doi: 10.3390/ijms20071723.

NIA H T， MUNN L L， JAIN R K. Physical traits of cancer. Science， 2020，370(6516): eaaz0868. doi: 10.1126/science.aaz0868.

SHI X H， ZHANG L Y， LI B， et al. The mechanical problems in tumor and tumor microenvironment. Adv Mech，2018，48: 360–409. doi: 10. 6052/1000-0992-16-039.

XIN Y， LI K， HUANG M， et al. Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine. Oncogene，2023，42(47): 3457–3490. doi: 10.1038/s41388-023-02844-x.


Refbacks

  • There are currently no refbacks.