Saliva-Exosomics in Cancer: Molecular Characterization of Cancer-Derived Exosomes in Saliva

Abstract

Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells and detected in saliva. Pathophysiological roles for salivary exosomes are beginning to be recognized in diseases including cancer, highlighting potential biomarkers and biological functions. Since early detection of cancer is vital for successful treatment, salivary exosomes would be advantageous in achieving a better survival rate due to their ready availability and noninvasiveness. The use of salivary exosomes may therefore be promising in the accurate detection of premalignant lesions and early-stage cancers, also for better our understanding of the molecular basis of tumorigenesis. In this chapter, we review our current knowledge of salivaomics, focusing on nucleic acids and proteins in saliva as potential cancer biomarkers. Since salivaomics is a rapidly evolving field, we hope to expand frameworks toward salivary exosomes, integrate new and existing information, and bridge salivaomics with other biomedical researches. Furthermore, we would like to coin the term “saliva-exosomics” as the next-generation salivaomics. Our goal in this chapter is to provide the most updated information on cancer-derived exosomes in the saliva as natural carriers of biomarkers and signaling molecules. Major advances include definitive structure analysis and molecular characterization of salivary exosomes. We also highlight the exosome biogenesis and cargo trafficking mechanisms in which recent animal studies have expanded our understanding of exosome-mediated transfer of cancer-derived products from distal tumor to salivary gland. The potential roles of the salivary exosomes in cancer progression and immune surveillance are also addressed.

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

“…One of the bottlenecks in the clinical application of EVs as drug carriers is that there is no uniform standard for the separation of EVs (Li et al, 2017;Merchant et al, 2017). EVs are widely found in blood (Ruivo et al, 2017), saliva (Nonaka & Wong, 2017), urine (Street et al, 2017), and other biological fluids as carriers of cellular information (Ferguson & Nguyen, 2016). Effective extraction and separation of these EVs from different sources for the purpose of drug delivery remain challenging (Nonaka & Wong, 2017;Street et al, 2017).…”

“…EVs are widely found in blood (Ruivo et al, 2017), saliva (Nonaka & Wong, 2017), urine (Street et al, 2017), and other biological fluids as carriers of cellular information (Ferguson & Nguyen, 2016). Effective extraction and separation of these EVs from different sources for the purpose of drug delivery remain challenging (Nonaka & Wong, 2017;Street et al, 2017). Hitherto, five separation methods have been developed for isolation of EVs: (1) ultracentrifugation-based isolation techniques;…”

A Role for Exosomes in Craniofacial Tissue Engineering and Regeneration

“…Exosomes isolated from glandular saliva were shown to possess miRNAs unique to salivary gland disease status (Michael et al, 2010). The use of salivary exosomes as biomarkers for cancer has been recently reviewed (Nonaka and Wong, 2017). Characterization of intact exosomes by FTIR distinguished exosomes of Oral Cancer subjects from Healthy individuals and suggests a noninvasive method for future diagnosis of oral cancer in early stages (Zlotogorski-Hurvitz et al, 2019).…”

Current Status of Magnetic Resonance on Saliva for Oral and Dental Health Early Diagnosis

“…Nuclear magnetic resonance (NMR) is an alternative and/or complimentary analytical method of great potential for the detection and analysis of biomarkers that are present in saliva, at the atomic level. Probing and characterization at the atomic level is of high importance for salivaomics, as it was recently observed that information in saliva is not only found in locally-produced molecules, but also carried from distant tissues through nano-vesicles [18]. NMR, as a powerful analytical method, can identify and quantitively analyze organic acids, amino acids, fatty acids, amines, and alcohol in the provided biofluid sample.…”