Crosstalk of Tumor Cells with Monocytes via Exosomes in Oral Cancer

Objectives: Although it has been shown that exosomes can play an active role in cellular communication and in different stages of cancer progression, the role of exosomes in oral squamous cell carcinoma (OSCC) pathogenesis. The objective of this study was to study the cross-talk of cancer cells with immune cells in OSCC. Methods: We performed a detailed analysis of the role of exosomes in tumor-immune-cell axis crosstalk. Results: We found that exosomes and oncogenic miRNAs (such as miRNA-21, miRNA-27) were detectable in higher quantities in the circulating exosomes and plasma of patients with OSCC. EVs isolated from the circulation of OSCC patients and OSCC cell lines showed comparable miRNA signatures, indicating the tumor origin of exosomes in the circulation of patients with OSCC. Challenging tumor cells with danger signals such as LPS and ethanol increased the production of exosomes and the release of oncogenic miRNAs. Fluorescently labeled exosomes from oral cancer cells were taken up by monocytes and caused activation of NF-κB and establishment of a pro-inflammatory and pro-tumorigenic milieu marked by increased levels of IL6, MCP1, PEG2 and MMP9.Series of experiments involving the introduction of exogenous oncogenic miRNA-21 analog induced a similar pro-inflammatory and pro-tumorigenic profile in monocytes, indicating the role of exosome-associated miRNA-21 in modulating the immune response in monocytes. Conclusions: In summary, our study describes a previously unknown pro-inflammatory circuit through which OSCC-derived EVs can induce the formation of pro-inflammatory phenotype in monocytes.