Stressors alter intercellular communication and exosome profile of nasopharyngeal carcinoma cells

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Exosomes and microvesicles (MVs) are nanometer‐sized membrane vesicles secreted from various cell types (including tumor cells) into the extracellular milieu and body fluids. MVs and exosomes contain different kinds of biomolecules, such as proteins, lipids, and nucleic acids, whereby EVs are suggested to modulate the immune function, angiogenesis, cell proliferation, cell‐to‐cell communication, and tumor invasion 1.
An increasing number of publications highlight the role of exosomes and microRNA carried by extracellular vesicles in tumor progression, metastatic activity, and also in tumor response under suboptimal conditions, for example, chemotherapy‐induced cell damage 3.
Head and neck cancers are a heterogeneous group of epithelial cancers (including the tumors of the larynx, hypopharynx, oropharynx, nasopharynx, the paranasal sinuses, and the oral and nasal cavity) that evolve from the oral and pharyngeal squamous epithelium.
Head and neck squamous cell carcinoma with an incidence of more than 600 000 per year is the sixth most common cancer worldwide 5. The five‐year survival rate for these patients is 50–60%, which has not decreased in the last thirty years 6.
Nasopharyngeal carcinoma (NPC) is a distinct cancer type of the head and neck region, differing from other cancers in terms of its epidemiology, etiology, clinical behavior, and response to treatment.
The prognosis of NPC depends on the metastatic activity and loco‐regional spread 7. Unfortunately, NPC has an early metastatic tendency 8. The metastatic potential is considerably high: 60–90% of the patients develop metastases in the regional lymphatic nodes 9.
In the background of this high metastatic activity may stand an additional mechanism of metastasis formation mediated by the exosomes produced by cancer cells 1.
NPC‐derived exosomes contain a variety of bioactive molecules, such as proteins, lipids, and nucleic acids like microRNAs (miRNAs). The latter are small, non‐coding post‐transcriptional regulators which are considered to play a key role in biological processes and tumor development. MiRNAs have been found to regulate many kinds of genes including development, proliferation, differentiation, and stress response 10.
MicroRNAs might also be good biomarkers for cancer detection, as miRNAs are remarkably stable in blood and it seems that each malignant disease has its own, specific miRNA expression profile 11. Being able to offer a reliable prognosis of NPC by miRNA characteristics would be a significant improvement in the battle against the disease.
The purpose of this study was to investigate how exosomal miRNAs might assist metastasis formation in NPC and how cytostatic therapies as stressors influence the characteristics of the tumor‐derived exosomes.
In our experimental model, we examined the exosome‐producing capacity of an NPC cell line under different cytostatic treatments. The miRNA content of the exosomes was also examined. We sought to answer whether cytostatic therapy could alter the quantity and contents of the tumor‐derived exosomes. 5‐8F NPC cells were exposed to two different types of cytostatic treatment, namely the classical chemotherapy with doxorubicin and a new method for the inhibition of cell proliferation, in which we utilized the photocatalytic activity of Ag–TiO2. The effects of these treatments were compared in terms of exosome output and miRNA profile.
Doxorubicin—the antracycline antibiotic widely used in the chemotherapy of several cancer types—exerts its cytostatic effect by intercalating the DNA.
Ag–TiO2 photocatalyst particles irradiated with exciting wavelength light show photocatalytic activity. Photocatalysis is a photo‐induced reaction, in which the photons are exiting the photocatalyst particles. During the photocatalytic process, the irradiated photocatalyst particles produce highly reactive oxygen species such as superoxide (O2−), hydrogen peroxide (H2O2), or hydroxyl radical (˙HO) 12. Due to these reactive radicals, the photocatalyst particles can degrade many organic compounds and inactivate microorganisms via destroying the cell wall and the DNA 12.
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