Characterization of the tumor amoeboid phenotype in cisplatin-resistant oral squamous cell carcinoma cell lines

• Grant number: 24/14597-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2024
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Camila de Oliveira Rodini Pegoraro
• Grantee: Laura Ribeiro da Silva
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Oral squamous cell carcinoma (OSCC) is the eighth most common type of cancer in the world, representing more than 90% of tumors in the head and neck region. Risk factors include smoking, excessive alcohol consumption and genetic predisposition. Despite advances in treatment and diagnosis, this disease still has high mortality rates due to late diagnosis, local recurrence and resistance to conventional therapies. Among these, cisplatin, a commonly used chemotherapy drug, is known to induce apoptosis and inhibit tumor proliferation. However, resistance to this drug is a significant challenge, especially due to the presence of cancer stem cells (CSCs) that have excellent self-renewal and differentiation capacity, also contributing to tumor recurrence and the emergence of more aggressive subpopulations. The plasticity of CSCs is evidenced by the epithelial-mesenchymal transition (EMT) and the amoeboid-mesenchymal transition (AMT), essential processes in tumor progression. In this context, AMT demonstrates a more invasive potential compared to EMT, in which CSCs adopt an amoeboid phenotype, characterized by highly mobile and rounded cells, capable of rapid morphological changes that impact cell migration patterns. This adaptability facilitates the processes of invasion, metastasis and resistance to conventional treatments. Considering that chemoresistance and the amoeboid phenotype have a significant impact on treatment failure, this study aims to characterize, in vitro, the amoeboid phenotype of two cisplatin-resistant CEB lines (SCC-9R and HSC-3R) and compare them with their non-resistant counterparts. The sublines will be evaluated and characterization will include immunofluorescence for the markers HOPX, PRRX1 and RTN1, qPCR to analyze the gene expression of these markers, in addition to functional assays of cell migration and invasion. We believe that the characterization of the amoeboid phenotype of cisplatin-resistant OSCC cell lines will provide support for the development of more effective therapies, improving the prognosis of patients.