Abstract
Exosomes are membrane-bound extracellular vesicles (EVs) that transport bioactive materials between cells and organs. The cargo delivered by exosomes can alter a wide range of cellular responses in recipient cells and play an important pathophysiological role in human cancers. In hepatocellular carcinoma (HCC), for example, adipocyte- and tumor-secreted factors contained in exosomes contribute to the creation of a chronic inflammatory state, which contributes to disease progression. The exosome-mediated crosstalk between adipocytes and liver cancer cells is a key aspect of a dynamic tumor microenvironment. In this review, we summarize the role of increased adiposity and the role of adipocyte-derived exosomes (AdExos) and HCC-derived exosomes (HCCExos) in the modulation of HCC progression. We also discuss recent advances regarding how malignant cells interact with the surrounding adipose tissue and employ exosomes to promote a more aggressive phenotype.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the most commonly occurring cancers in both men and women worldwide [1]
Endosomal Sorting Complex Required for Transport (ESCRT) II, in turn, initiates the oligomerization and formation of the ESCRT III complex (Figure 2). Exosomal proteins such as Alix are associated with ESCRT through the tumor suppressor susceptibility gene 101 (TSG101), charged multivesicular protein body 4 (CHMP4), and other proteins that are involved in the budding process and exosomal cargo selection [47]
We analyzed the association between obesity and adipose-derived factors and their role in HCC progression
Summary
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the most commonly occurring cancers in both men and women worldwide [1]. The incidence of HCC is rapidly increasing, compared to any other cancer in the United States, as a result of modifiable behaviors such as excess nutrition, increased alcohol consumption, smoking, and chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) [2]. The link between increased adiposity and liver diseases, such as NAFLD and AFLD, Cells 2020, 9, 1988; doi:10.3390/cells9091988 www.mdpi.com/journal/cells morphological features (Figure 1). The capacity of adipocytes to store excess fat is not unlimited, and chronic increased fat intake and low energy expenditure can cause lipids to accumulate in organs such as the liver, rather than in the adipose tissue [11]. BAT and beige fat have functions distinct from WAT, and are highly metabolically active [14]. Origins regionsadipogenesis of WAT, BAT androle beige fat areinalso distinct [14]. of WAT can be differentiated from mesenchymal cells after the postnatal period in response to excess energy
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