THE ROLE OF MACROPHAGES EXTRACELLULAR VESICLES IN THE BIOLOGICAL BEHAVIOR OF TONGUE SQUAMOUS CELL CARCINOMA
Tumor Microenvironment; Carcinoma, Squamous Cell; Curcumin; Cell Culture Techniques.
Cancer is a worldwide health problem and the cases that affect oral cavity are among the types that have the highest incidences, being represented by oral squamous cell carcinoma (OSCC) in more than 90% of cases. Among the different types of OSCC, the tongue squamous cell carcinoma (TSCC) are the most common and often related to higher chances of local invasion, metastasis and worse prognosis. Currently, cancer is thought to consist of malignant cells associated with different types of surrounding cells, forming the tumor microenvironment (TME). Thus, investing in therapeutic studies related to cell responses, such as, tumor-associated macrophages (TAMs), seems to be an interesting alternative since they are genetically more stable. TAMs may have two different phenotypes: the classically activated M1 (M1 Mfs), which exhibits antitumor behavior, and the alternatively activated or M2 phenotype (M2 Mfs), which have a pro-tumor profile. Both types of Mfs release extracellular vesicles (EVs) with nanomeric size, specialized in cell-cell communication, transporting proteins, RNA, DNA and lipids, and they are also considered as an effective vehicle in drug delivery. These EVs can be loaded with curcumin (CUR), which is a drug derived from Curcuma longa rhizome. CUR is effective in therapy against TSCC, decreasing proliferation rates, leading to evasion of apoptosis, and decreasing the potential for migration and invasion of the malignant cells. Therefore, the aim of this study is evaluate through functional proliferation and migration assays, the role of EVs derived from Mfs on TSCC cells. Also, evaluate the therapeutic efficacy of CUR associated with EVs derived from Mfs (CUR-EVs) in comparison to the application of free CUR, attempting to identify, in vitro, which form of use of this substance is more effective in TSCC regarding to the biological behavior of the malignant cells.