In vitro effects of osteoblast-derived osteopontin on autophagy process in human oral squamous cell carcinoma cells

• Grant number: 19/03585-6
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2019
• End date: September 30, 2022
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Lucas Novaes Teixeira
• Grantee: Lucas Novaes Teixeira
• Host Institution: Centro de Pesquisas Odontológicas São Leopoldo Mandic. Faculdade São Leopoldo Mandic (SLMANDIC). Sociedade Regional de Ensino e Saúde S/S Ltda (SRES). Campinas , SP, Brazil
• Associated researchers: Elizabeth Ferreira Martinez ; Larissa Moreira Spinola de Castro Raucci ; Paulo Tambasco de Oliveira ; Vera Cavalcanti de Araujo

Abstract

Squamous cell carcinoma (SCC) is the most prevalent malignant neoplasm of the oral structures, which may invade and destroy bone tissue due to increased osteoclastic activity. The matricelular protein osteopontin (OPN) has been associated with more aggressive tumors since OPN can promote cell adhesion, proliferation, and invasion. In bone, OPN is the most abundant non-collagenous protein, especially concentrated at bone interfaces (cement lines and the lamina limitans), and play important roles in osteoblast and osteoclast adhesion and function. Teixeira et al. (2016) have demonstrated that osteoblast-derived OPN affects the interactions among oral SCC-derived epithelial cells, osteoblasts, and osteoclasts, which could contribute to the process of bone destruction during bone invasion by oral SCC. The role of osteoblast-derived OPN on the autophagy process in oral SCC cells, however, is not fully understood. In this context, the present study aims to evaluate the effects of osteoblast-derived OPN in cocultures of osteoblastic cells and oral SCC and its effects on the autophagy process in oral SCC. It will be evaluated: 1) autophagic flux by means of Beclin-1, p62 e LC3 quantification by western blotting in oral SCC cells cocultured with osteoblastic cells; 2) signaling pathways involved in autophagy modulation mediated by osteoblast-derived OPN in oral SCC cell cultures and 3) the role of alphaVbeta3 integrin and CD44 receptor on autophagy-mediated by osteoblast-derived OPN in oral SCC cell cultures. (AU)