Effect of oral cancer cell-derived extracellular vesicles in the macrophages differentiation

Abstract

In recent years, the tumor microenvironment received significant attention from researchers, since the cells that compose it (neoplastic or not) are in a dynamic state of interaction with cancer cells, creating a favorable environment for tumor development. Tumor-Associated Macrophages (TAM) also residing in this microenvironment and comprise different cell subtypes, being that the M2 subtype is more prevalent. M2 macrophages are associated with increased angiogenesis by stimulating tissue remodeling and degradation of extracellular matrix components, inducing immunological tolerance and thus, support the development of neoplastic cells. Although the mechanisms involved in immune cells modulation during tumor development are still not well known, recently extracellular vesicles (EVs) has taken an important physiological and pathological role in cell-cell communication through interactions mediated by receptors or by transfer of bioactive molecules such as receptors, proteins, lipids, tRNA, mRNA, microRNA, and organelles, by changing the phenotype of the recipient cell. Tumor cells can transfer information to different cell types using EV as a vehicle, changing characteristics of the tumor microenvironment and establishing a metastatic niche. Thus, this study aims to analyze: 1) the role of EVs in differentiation and modulation of monocyte and macrophages activity, using i) EVs from cell lines SCC-9 (oral cancer cells of primary site), HSC-3 (oral cancer cells of metastatic site) and HaCaT (normal keratinocytes); ii) samples of oral cancer-, inflammatory fibrous hyperplasia-, and normal oral mucosa-derived EVs 2) using proteomic approaches to identify proteins in these vesicles in order to understand their possible role in cell phenotype modulation and oral cancer progression. (AU)