Characterization of cancer stem cell phenotype in cisplatin-resistant oral squamous cell carcinoma cell lines

Author(s)

Talita Fonseca Frazon

• Document type: Master's Dissertation
• Press: Bauru.
• Institution: Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB)
• Defense date: 2024-04-15

Examining board members

Camila de Oliveira Rodini Pegoraro; Nádia Ghinelli Amôr; Vanessa Soares Lara; Everton Freitas de Morais

• Advisor: Camila de Oliveira Rodini Pegoraro

Abstract

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide, and has high rates of morbidity and mortality associated with late diagnosis, local recurrence and metastasis in cervical lymph nodes. Studies suggest the presence of a subpopulation of tumor cells with limited prescription capacity, capable of self-renewal and differentiation, called cancer stem cells (CSC). Furthermore, this subpopulation is considered responsible for the emergence, progression and tumor chemoresistance in different carcinomas, including oral carcinomas. Among the treatments used, surgical resection associated with radio and chemotherapy is the most frequently recommended approach. However, studies show that CSC are resistant to the main chemotherapy used to treat OSCC, cisplatin. Consequently, only differentiated tumor cells are eliminated while CSC remain quiescent, strongly contributing to tumor recurrence and the predominance of more resistant and aggressive tumor cell subpopulations. Considering that chemoresistance is one of the main causes of OSCC treatment failure, the purpose of this work was to develop and characterize subpopulations of tumor cells resistant to cisplatin in vitro. For this purpose, the parental OSCC lines SCC-9 and HSC-3 were used, and MTS cytotoxicity assays were used to develop cisplatin-resistant sublines. Our findings demonstrated a high percentage of CD44highESAlow in resistant lines, as well as significant morphological and gene expression changes of the VIMENTIN and TWIST markers through PCR, related to the EMT induction process. Even so, it was possible to observe that the sphere formation capacity was impaired and markers such as CD44, ALDH1 and ABCs were regulated at levels in the resistant SCC-9 lineage. Our results support the characterization of strains resistant to cisplatin treatment, offering support for studies and therapeutic strategies based on the development of more efficient targeted therapies and/or adjuvants that, ultimately, result in a better prognosis for patients with OSCC. (AU)

• FAPESP's process: 21/15066-3 - Characterization of cancer stem cell phenotype in cisplatin-resistant oral squamous cell carcinoma cell lines
• Grantee: Talita Fonseca Frazon
• Support Opportunities: Scholarships in Brazil - Master