Association of extracellular vesicles derived from fibroblasts with the progression of Oral Squamous Cell Carcinoma

Abstract

The Cancer-Associated Fibroblast (CAFs) represent the main cellular components of the tumor microenvironment of many Carcinomas. In oral Squamous Cell Carcinoma (OSCC), the most common tumor of the oral cavity, CAF have been shown to promote tumor cell migration and invasion, proliferation, adhesion, immunosuppression, angiogenesis and worsen the patients' prognosis. Cancer-derived EV exert and play an important role in the signaling between the epithelium and stroma during the malignant transformation and tumoral progression. EVs are a heterogeneous group of nanometer-sized circulating particles composed of a lipid bilayer and loaded with transmembrane and cytosolic proteins as well as DNA and different types of RNA. Notably, the emerging evidence suggests that EV derived from tumor microenvironment may modulate recipient cells, contributing to the formation of a highly complex stroma able to modulate the invasive and metastatic potential of the cancer cells. To better understand the role of CAFs within the tumor stroma during the development of OSCC, this project aims to identify molecular signatures for of tumor progression through the proteomic study of fibroblasts-derived extracellular vesicles from primary fibroblasts from normal oral mucosa, oral potentially malignant disorders and OSCC. In addition, will be evaluated the effects of CAF-EV on OSCC cell invasion, proliferation, epithelial-mesenchymal transition of cell lines HMK, DOK, SCC-9 and HSC-3. It is expected (i) characterize the proteins associated with tumor progression; (ii) evaluate their correlation with the clinical characteristics of the patients and (iii) evaluate the functional role of the EVs derived from cancer-associated fibroblasts and the molecular mechanisms involved in the progression of oral OSCC. (AU)