Exosomes as the Promising Biomarker for Epstein-Barr Virus (EBV)-Associated Cancers

Abstract

Exosomes are microvesicles with sizes ranging from 50 to 150 nm. These small vesicles are known to morphologically and functionally resemble virus particles from human immunodeficiency virus type I (HIV-I) and human T-lymphotropic virus type I (HTLV-I). The function of exosomes is to mainly mediate cell-to-cell communication by exchanging various macromolecules including proteins, lipids and nucleic acids in diverse cellular processes. Due to its size and structural simplicity, the transfer of pathogenic or virulent cellular factors across the cells mediated by exosomes is more efficient, hence facilitating the dissemination of viral infections and cancer diseases. The pathogenic role of exosomes in various cancers such as lung and breast, and their potentials as biomarkers have been previously studied, yet limited information is known for Epstein-Barr virus (EBV)-associated cancers. In this chapter, we discuss current evidences that support the pathogenic roles of exosomes in EBV-related cancers and their potentials as biomarkers in cancer diagnostics and therapy response. Here, we also highlight the potential challenges in the development of exosome-based biomarkers for clinical application.

Recent Advances in Diagnostic Approaches for Epstein–Barr Virus

“…Exosomes are extracellular microvesicles surrounded by a lipid bilayer membrane that is strengthened with macromolecules such as lipids, carbohydrates, proteins, and nucleic acids (microRNA (miRNA), mRNA, and DNA) with size ranging from 30 to 150 nm in diameter and densities of 1.13-1.21 g/mL [71]. These microvesicles are usually released from most eukaryotic cell types, including dendritic cells, epithelial cells, endothelial cells, T cells, B cells, reticulocytes, neurons, and cancerous cells [71,72]. In addition, exosomes are present and can be detected in almost all body biological fluids, such as serum, plasma, semen, breast milk, cerebrospinal fluid, urine, saliva, ascites fluid, amniotic fluid, and bronchoalveolar lavage fluid [71,72].…”

“…These microvesicles are usually released from most eukaryotic cell types, including dendritic cells, epithelial cells, endothelial cells, T cells, B cells, reticulocytes, neurons, and cancerous cells [71,72]. In addition, exosomes are present and can be detected in almost all body biological fluids, such as serum, plasma, semen, breast milk, cerebrospinal fluid, urine, saliva, ascites fluid, amniotic fluid, and bronchoalveolar lavage fluid [71,72]. Currently, exosomes have been reported to have a critical role in cell to cell communication due to a unique lipid bilayer membrane's exosome components [71,72].…”

“…In addition, exosomes are present and can be detected in almost all body biological fluids, such as serum, plasma, semen, breast milk, cerebrospinal fluid, urine, saliva, ascites fluid, amniotic fluid, and bronchoalveolar lavage fluid [71,72]. Currently, exosomes have been reported to have a critical role in cell to cell communication due to a unique lipid bilayer membrane's exosome components [71,72]. It has been shown that exosomes play important role in the pathogenesis of several viral diseases, such as EBV, herpes simplex virus, HIV-1, hepatitis C and human T-cell lymphotropic virus type 1 (HTLV-1), and in the pathogenesis of different cancers, such as lymphoma, melanoma, glioma, NPC, gastric carcinoma, colorectal cancer, and breast and ovarian cancers [71,73].…”

“…They have critical roles in different biological and pathological processes, such as cell proliferation, evasion from the immune system, angiogenesis, carcinogenesis, and metastasis [73]. EBV exosomes have been found to embed different types of viral components such as LMP1, LMP2A, BamHI-A rightward frame 1 (BARF1), and EBV nucleic acid (DNA, mRNA, and miRNA) [71][72][73]. Hence, these EBV exosomes targets can be helpful diagnostic and prognostic markers, as well as anticancer target therapies in different types of EBV-associated carcinomas and diseases (Figure 1).…”

“…detection of different pathogenic markers on exosomes could be employed as a sensitive and specific diagnostic method, as well as in monitoring treatment response in different EBV-associated carcinomas. The molecular technique of qPCR is an ideal method for this detection, especially in detecting EBV mRNAs and EBV miRNAs, which are more stable than other EBV pathogenic genes and proteins because they are both encapsulated inside the exosomes and protected from ribonuclease (RNase) degradation [71]. Currently, exosome detection has several limitations, including low specificity and sensitivity.…”