Characterization of the functional relationship between macrophages, cancer stem cells and epithelial-to-mesenchymal transition in oral squamous cell carcinoma

• Ano de defesa: 2019
• Autor(a) principal: Amôr, Nádia Ghinelli
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Carcinoma Epidermóide; Células-Tronco Neoplásicas; Epithelial-Mesenchymal Transition; Fator de Crescimento Transformador beta; Macrófagos; Macrophages; Neoplastic Stem Cells; Squamous cell carcinoma; Transforming Growth Factor beta; Transição Epitelial-Mesenquimal
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/25/25149/tde-04102021-153616/

Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms of the head and neck, and the major prognostic factor is the presence of metastatic lesions in cervical lymph nodes. Studies have shown that cancer stem cells (CSCs) might be involved with migration and invasion process through the epithelial-to-mesenchymal transition (EMT) in tumor cells. It is known that cellular and soluble components of tumor microenvironment influence the EMT process, and macrophages represent the major class of cells that are recruited to the tumor site in different cancers. Furthermore, TGF- signaling has been described as a critical regulator of EMT in cancer cells and can sustain CSCs properties. In view of that, the purpose of this study was to determine the functional relationship between CSC, EMT, and macrophages in OSCC. In paper 1, we analyzed the in vitro and in vivo behavior of two CSCs subpopulations, CD44HighESALow and CD44HighESAHigh sorted from the OSCC cell line, LUC4. Our findings suggested that the subpopulation CD44HighESAHigh is the one that carries the most stemness features. However, what induced or sustained that phenotype remained to be clarified. In paper 2, the influence of macrophages on CSCs was analyzed by directly co-culturing the subpopulations of CSC with macrophages or culturing CSC with conditioned medium from macrophages. Our results suggested that macrophages promote EMT in CSC, and that influence was probably mediated by TGF- signaling. Altogether, our results showed that tumor heterogeneity must be considered and deeply characterized to better determine the therapeutic approach.