Effects of different types of emotional stress on oral cancer progression: a translational study exploring the role of systemic endocrine and immunological mediators

• Grant number: 24/23171-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Daniel Galera Bernabé
• Grantee: Diovana de Melo Cardoso
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Oral cancer is one of the most common malignancies worldwide, mainly in countries with a medium or low Human Development Index. Evidence from our research team and other investigations suggests that psychological stress and its hormonal mediators can influence cancer progression. Additionally, it has been shown that stress can modulate the secretion of pro-inflammatory cytokines in the bloodstream and in the tumor microenvironment. The goal of the present study is to evaluate the effects of emotional stress and its mediators on the oral squamous cell carcinoma (OSCC) cells behavior using a novel translational experimental model in humans. SCC9 and SCC25 cells, derived from OSCC, will be treated with serum derived from individuals subjected to four different types of emotional stress using a new experimental protocol developed by our research team. Serum from individuals exposed to different stress protocols will be evaluated for norepinephrine, epinephrine, cortisol, IL-6 and TNF-alpha concentrations. After 24 hours of exposure to serum derived from volunteers before and after emotional stress stimuli, the cells will be evaluated for proliferation, migration, invasion and apoptosis. The role of beta-adrenergic receptors, glucocorticoid receptors, IL-6, TNF-alpha, as well as the PKA and NF-kappa B signaling pathways in tumor progression induced by stress hormones and pro-inflammatory cytokines will be evaluated by immunofluorescence, inhibition assays and functional assays. Specific statistical tests will be used to evaluate the influence of stress-modulated hormonal and inflammatory mediators and the molecular pathways involved on the various behavioral outcomes of tumor cells. We hope that the results from the present study will demonstrate for the first time a direct relationship between emotional stress in humans and the oral cancer progression, with insights into the psycho-endocrine-immunological pathways involved and which may become potential therapeutic targets.