Microscopic and immunohistochemical characterization of tumor development in immunocompromised mice xenografted with cancer stem cells of oral squamous cell carcinoma

• Ano de defesa: 2020
• Autor(a) principal: Buzo, Rodrigo Fonseca
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Animal model; Carcinoma epidermóide; Células-tronco neoplásicas; Epithelial-mesenchymal transition; Modelo animal; Neoplastic stem cells; Squamous cell carcinoma; Transição epitelial- mesenquimal
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/25/25149/tde-26102021-091418/

Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms of the head and neck region, with overall survival <5 years. The worst prognosis of the disease is lymph node metastasis associated with a subpopulation of stem cells in tumors, known as cancer stem cells (CSC). Studies have shown that this subpopulation undergoes epithelial to mesenchymal transition (EMT), a process which epithelial cells acquire a mesenchymal phenotype. In OSCC, CSC can be identified by biomarkers, CD44 transmembrane protein being the most commonly used. In oral cancer research, animal models have been widely used as a strategy to understand carcinogenesis as well as to test new antineoplastic agents and to develop new therapeutic approaches. We aimed to evaluate and compare microscopically murine tumors induced by CSC xenotransplantation. Two subpopulations CD44HighESAHigh (epithelial) and CD44HighESALow (mensenchymal) were isolated from OSCC cell line LUC4 by flow cytometry (BD FACSAria Fusion). Xenotransplantation was performed with 5x103 cells injected in the tongue into two groups with twelve NOD/SCID mice each one. Forty-nine days post-injection, tumors were measured, collected and submitted to histotechnical processing for microscopic and immunohistochemical analyses. CD44HighESAHigh cells showed great tumorigenic potential, being able to originate larger tumors in twelve animals (average tumor area: 4.22 mm²). In contrast, only six animals (50%) xenografted with CD44highESAlow cells developed microscopically visible tumors (average tumor area: 0.20 mm²). Structural and cellular changes similar to the human OSCC were observed in both groups. In addition, animals xenografted with CD44HighESAHigh cells showed greater weight loss compared to the CD44HighESALow group (p = 0.0217). The correlation of CSC subpopulations with their corresponding tumors in vivo represents a reliable approach for future research in oral cancer, highlighting the role of different CSC phenotypes in OSCC development and progression. Further studies should be conduct in this field, for example, in understanding how they respond in commonly used therapeutics and develop techniques to overcome their resistance mechanisms.