The role of extracellular vesicles from different origin in the microenvironment of head and neck cancers

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.

B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role

“…In recent years, the role of extracellular vesicles (EVs) in tumor progression has become an interesting area of research for understanding and combating cancer. In cancer, EVs mediate the transfer of oncogenic proteins, nucleic acids, and lipids from tumor cells to other tumor cells and the surrounding microenvironment [ 1 , 2 , 3 ]. Recent classification of EVs has led to distinctions based on size (exosomes: 30–100 nm, microvesicles: 100–1000 nm, oncosomes: 1000–10,000 nm) [ 4 ].…”

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

“…EVs are a class of phospholipid-bilayer-enclosed membranes carrying a variety of biological molecules, including nucleic acids, proteins, and lipids. EVs are released by virtually all cell types in an evolutionarily conserved manner across eukaryotes and prokaryotes [62,63]. EVs can act on local and distant sites and can be found circulating in a wide range of biological fluids, including blood, urine, bile, nasal secretions, and saliva [64].…”

“…The most well-characterized pathway for ILV biogenesis is through an endosomal sorting complex required for transport (ESCRT) complex-dependent mechanism. ESCRT (-0, -I, -II) recognizes and sequesters ubiquitinated proteins on the endosomal membrane, followed by inward budding and scission by ESCRT-III [63,66]. Cargo clustering may also occur through syntenin along with the ESCRT accessory protein ALG-2-interacting protein X (ALIX), with only ESCRT-III being required for ILV biogenesis [67,68].…”

Extracellular Vesicles Released by Tumor Endothelial Cells Spread Immunosuppressive and Transforming Signals Through Various Recipient Cells

“…At present, limited information is available on the cellular and Abbreviations: ACTB, actin beta 1; ASCs, adipose stem cells; CD14, cluster of differentiation 14; CD31, cluster of differentiation 31; CD47, cluster of differentiation 47; CD73, cluster of differentiation 73; CD90, cluster of differentiation 90; CD105, cluster of differentiation 105; CD163, cluster of differentiation 163; CD206, cluster of differentiation 206; CM, conditioned medium; Ctr, control; DMEM, Dulbecco's modified Eagle medium; DMSO, dimethyl sulfoxide; ELISA, enzyme-linked immunosorbent assay; EVs, extracellular vesicles; FACS, fluorescence-activated cell sorting; FBS, fetal bovine serum; HLA, human leukocyte antigen; HMEC, human dermal microvascular endothelium; HNSCC, head and neck squamous cell carcinoma; IFN-γ, interferon gamma; IL-6, interleukin 6; IL-10, interleukin 10; lncRNA, long non-coding RNA; MALAT1, metastasis associated lung adenocarcinoma transcript 1; MHC, major histocompatibility complex; PBMC, peripheral blood mononuclear cell; PBS, phosphate-buffered saline; RNA, ribonucleic acid; RT-PCR, reverse transcription polymerase chain reaction; TECs, tumor endothelial cells; TGF-β1, transforming growth factor beta-1; Th1, T helper type 1; Th17, T helper type 17; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor alpha; Treg, T regulatory cells; Trtm, treatment; VEGF, vascular endothelial growth factor. molecular functions of TEC from HNSCC and EV released by those cells (Rodriguez Zorrilla et al, 2019;Xie et al, 2019). Studying the TEC-EV molecular composition and specific functions in tumor development can define novel mechanisms of cancer immune editing, help developing novel therapeutic targets, and determine diagnostic signatures to be used for noninvasive liquid biopsies.…”