Abstract
Simple SummaryExtracellular vesicles (EVs) are particles naturally released from cells and mediate intercellular communication. Recently, emerging studies have shown that EVs play a crucial role in regulating progression of hepatocellular carcinoma (HCC), which is one of the leading causes of cancer-related death worldwide. With the advances of technologies in isolating EVs from patients’ blood, EVs are regarded as promising biomarkers for detecting HCC at an earlier stage. This review provides an overview of the current EVs isolation methods, the biological roles of EVs in mediating disease progression, and the feasibility of EVs’ use for detection of HCC. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and one of the leading causes of cancer-related death worldwide. Despite the improvements in surveillance and treatment, the prognosis of HCC remains poor. Extracellular vesicles (EVs) are a heterogeneous group of phospholipid bilayer-enclosed particles circulating in the bloodstream and mediating intercellular communication. Emerging studies have shown that EVs play a crucial role in regulating the proliferation, immune escape, and metastasis of HCC. In addition, because EVs are present in the circulation at relatively early stages of disease, they are getting attention as an attractive biomarker for HCC detection. Over the past decade, dedicated efforts have been made to isolate EVs more efficiently and make them useful tools in different clinical settings. In this review article, we provide an overview of the EVs isolation methods and highlight the role of EVs as mediators in the pathogenesis and progression of HCC. Lastly, we summarize the potential applications of EVs in early-stage HCC detection.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy (>80% cases) and ranks sixth for cancer incidence and third for cancer-related death worldwide [1,2]
Extracellular vesicles (EVs), (2) nanostructured substrates increase the surface interacting with EVs, and (3) click chemistry(TCO/TZ interaction) and disulfide cleavage lead to DTT-driven EVs release, which results in isolation of HCC-derived EVs mediated EVs capture (TCO/TZ interaction) and disulfide cleavage lead to DTT-driven EVs release, with high purity
Using the fluorescence-activated cell scanning, Julich-Haertel et al identified a subgroup of EVs, the epithelial cell adhesion molecule (EpCAM)+ asialoglycoprotein receptor 1+ (ASGPR1)+ EVs, which is capable of distinguishing HCC from cirrhosis with an area under the curve (AUC) of 0.73 [13]
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy (>80% cases) and ranks sixth for cancer incidence and third for cancer-related death worldwide [1,2]. Biomarkers that could sensitively detect early-stage HCC have been under investigation [4]. Extracellular vesicles (EVs) are a heterogeneous group of phospholipid bilayer-enclosed particles that are released by both tumor and normal cells [6]. The quantity of EVs is 2.3- to 3.0-fold higher in HCC cases than in cirrhosis controls [12,13], making them ideal biomarkers for non-invasive diagnosis of liver cancer. We summarize the EVs detection technology, role of EVs in cancer cell proliferation, angiogenesis, and metastasis of HCC, and the feasibility of EVs’ use as a diagnostic biomarker for HCC
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