Abstract
Simple SummaryHead and neck squamous cell carcinomas (HNSCC) are a challenging group of malignancies that require a multidisciplinary management approach and where advances in targeted therapeutics remain relatively meager. Despite these challenges, recent advances in immunotherapeutic approaches have positively affected the clinical outcome for patients with advanced disease. Novel approaches for systemic therapy continue, however, to be an urgent need for this disease. This review highlights the possible role of exosomes in sustaining malignant cells in HNSCC and the prospects of future therapeutic interventions in these cellular components based on current evidence.Head and neck squamous cell carcinoma (HNSCC) represents an aggressive and heterogenous group of cancers whose pathologies remain largely unresolved. Despite recent advances in HNSCC therapeutic strategies, the overall survival of HNSCC patients remains poor and continues to prompt efforts to develop more effective therapies. Exosomes are a subtype of extracellular vesicles secreted by a variety of cells that have begun to spark significant interest in their roles in cancer. As membranous vesicles, spanning from 30–150 nm in diameter, exosomes mediate the transport of various molecules, such as proteins, nucleic acids, and lipids, intercellularly throughout the body. In doing so, exosomes not only act to deliver materials to cancer cells but also as signals that can confer their progression. Accumulating evidence shows the direct correlation between exosomes and the aggressiveness of HNSCC. However, more research is warranted in this field to further our understanding. In this review, we attempt to highlight the tumor-supporting roles and therapeutic potential of exosomes in HNSCC. We introduce first the biogenesis and component features of exosomes, followed by their involvement in HNSCC proliferation and metastasis. We then move on to discuss HNSCC-derived exosomes’ influence on the tumor microenvironment and their function in tumor drug resistance. Finally, we explore the promising potential of exosomes as HNSCC biomarkers and therapeutic targets and drug carriers for HNSCC treatments.
Highlights
Head and neck cancer is the sixth most common cancer worldwide [1,2,3]
Many studies have demonstrated that mRNAs, miRNAs, and other noncoding RNAs are contained in exosomes. Chiba and his colleagues found that exosomes derived from colorectal cancer cells contained mRNAs, miRNAs, and natural antisense RNAs were delivered into recipient cells to support tumor development [28]
Ludwig et al isolated exosomes by sizeexclusion chromatography from the plasma of 38 Head and neck squamous cell carcinoma (HNSCC) patients and 14 healthy donors and measured exosome-mediated effects on the functions of normal human lymphocyte subsets and natural killer (NK) cells [43]. They found that the presence, quantity, and molecular content of isolated, plasma-derived exosomes discriminated HNSCC patients with active disease (AD) from those with no evident disease (NED) after oncological therapies
Summary
90% of all head and neck cancers are classified as head and neck squamous cell carcinoma (HNSCC), with a high frequency of tumor recurrence/metastasis and low patient survival. Exosomes are small membranous vesicles that act as intercellular messengers through the cargo they carry These discoid vesicles are 30–150 nm in diameter and secreted by living cells from early endosomes containing a typical lipid bilayer structure [5]. Their distribution is widespread, and they are found in various bodily fluids, such as serum, plasma, saliva, urine, and amniotic fluid [6]. The biological origins of exosomes begin with early endosomes, which form through plasma membrane invagination During this process, extracellular components and cell membrane proteins are encapsulated, and inward budding of the early endosome’s membrane leads to the formation of an exosomal vesicle. Exosomes isolated from individual salivary glands are derived from cells within that specific gland (including parotid, submandibular, and sublingual), which may reflect the physiologic state of the gland at
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