Tumor‐derived exosomes and microvesicles in head and neck cancer: Implications for tumor biology and biomarker discovery

Abstract

Exosomes and microvesicles (MVs) are nanometer-sized, membranous vesicles secreted from many cell types into their surrounding extracellular space and into body fluids. These two classes of extracellular vesicles are regarded as a novel mechanism through which cancer cells, including virally infected cancer cells, regulate their micro-environment via the horizontal transfer of bioactive molecules: proteins, lipids, and nucleic acids (DNA, mRNA, micro-RNAs; oncogenic cargo hence often referred to as oncosomes). In head and neck cancer (HNC), exosomes and MVs have been described in Epstein Barr Virus (EBV)-associated nasopharyngeal cancer (NPC), as well as being positively correlated with oral squamous cell carcinoma (OSCC) progression. It has therefore been suggested that HNC-derived vesicles could represent a useful source for biomarker discovery, enriched in tumor antigens and cargo; hence fundamentally important for cancer progression. This current review offers an overall perspective on the roles of exosomes and MVs in HNC biology, focusing on EBV-associated NPC and OSCC. We also highlight the importance of saliva as a proximal and easily accessible bio-fluid for HNC detection, and propose that salivary vesicles might serve as an alternative model in the discovery of novel HNC biomarkers.

Membrane transporters in salivary exosomes and microvesicles as biomarkers of systemic or oral disease

“…Exosomes have been identified in body fluids, such as breast milk, blood, urine, semen, amniotic fluid, ascites fluid, and saliva [4]. Exosomes participate in intercellular communication [31][32][33], immune regulatory functions [34], transport of morphogens and RNA [35][36][37], and tumor metastasis [38].…”

“…Salivary exosomes have been shown to be useful in detecting diseases, such as Sjögren's syndrome [41], as well as head and neck cancer [38].…”

“…Salivary microvesicles have been shown to be potentially useful in detecting breast cancer [45], as well as head and neck cancer [38].…”

Is Salivary Exosome the Answer to Early Detection of Oral Cancer?

“…2 Human saliva is an ideal fluid for developing non-invasive diagnostics and salivary biomarkers have been demonstrated in clinical studies showing promising diagnostic potentials but lacking in sensitivity mostly due to complexity of saliva. 2,3 Hence, this led to the emerging interests on exosomes which are membrane-bound extracellular vesicles carrying specific membrane proteins with numerous types of nucleic acids 4 and protein cargos, 2,5,6 well protected from degradation by extracellular enzymes. Their size (50-150 nm diameter) is an advantage for purification and reducing the overall complexity of saliva.…”

“…2 Emerging studies began looking at biochemical properties of disease-derived saliva exosomes. 2,5,6 So, it seems no brainer that salivary exosome serves as the perfect target for finding a biomarker that could enable early oral cancer detection by means of a simple saliva test.…”