Abstract
The proliferation and metastasis ability of tumors are mediate by the "mutual dialogue" between cells in the tumor microenvironment (TME). Extracellular vesicles (EVs), mainly exosomes and microvesicles, play an important role in achieving intercellular substance transport and information transfer in the TME. Initially considered "garbage dumpsters" and later referred to as "signal boxes", EVs carry "cargo" (proteins, lipids, or nucleic acids) that can redirect the function of a recipient cell. Currently, the molecular mechanisms and clinical applications of EVs in head and neck cancers (HNCs) are still at an early stage and need to be further investigate. In this review, we provide insight into the TME of HNCs, classifying and summarizing EVs derived from different cell types and illuminating their complex signaling networks involved in mediating tumor proliferation, invasion and metastasis, vascular angiogenesis and cancer drug resistance. In addition, we highlight the application of EVs in HNCs, underlining the special pathological and physiological environment of HNCs. The application of tumor heterogeneous EVs in saliva and circulating blood diagnostics will provide a new perspective for the early screening, real-time monitoring and prognostic risk assessment of HNCs. Given the concept of precise and individual therapy, nanostructured EVs are equipped with superior characteristics of biocompatibility, low immunogenicity, loadability and modification ability, making these molecules one of the new strategies for HNCs treatment.
Highlights
Head and neck cancers (HNCs) is one of the most common malignant tumors in the world
HNC-derived extracellular vesicles (EVs) mediate the bidirectional regulation of tumor immunity, suggesting that future immunotherapy may be based on the tumor microenvironment or individualized treatment of circulating EVs
Protein profiling revealed that the high expression of MFAP5, a protein component of extracellular microfibrils, in Cancer-associated fibroblasts (CAFs)-derived exosomes triggers the activation of MAPK and AKT serine/threonine kinase (AKT) signaling pathways and promotes the proliferation and metastasis of Oral Squamous Cell Carcinoma (OSCC) cells [121] (Fig. 3a)
Summary
Head and neck cancers (HNCs) is one of the most common malignant tumors in the world. The EVs derived from HNC cell can promote the malignant phenotype of tumor cells by delivering exosomal PFKFB3, Shh and other angiogenic proteins and activating the relevant model pathway to induce endothelial proliferation and tube formation [95, 96].
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