Isolation and characterization of oral cancer stem cells in primary lesions and peripheral blood: role of the phenotypic plasticity in the process of metastasi

• Ano de defesa: 2022
• Autor(a) principal: Lopes, Nathália Martins
• 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: Cancer stem cells; Carcinoma epidermóide de boca; Células tumorais circulantes; Células-tronco de câncer; Circulating tumor cells; Citometria de fluxo; Epithelial-mesenchymal transition; Flow cytometry; Oral squamous cell carcinoma; Phenotypical plasticity; Plasticidade fenotípica; Transição epitélio-mesenquimal
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/25/25149/tde-19052022-100909/

Recent evidence shows that mechanisms of tumor recurrence and metastasis, as well as failure to treat oral squamous cell carcinoma (OSCC), are due, among other factors, to the patterns of cellular heterogeneity present in tumors that can be explained by the model of cancer stem cells (CSC). It is also known that there is a link between CSC and the epithelial-mesenchymal transition (EMT) process, which explains the greater capacity of migration and metastatic potential of CSCs compared to the other tumor cells. In addition, when tumor cells detach from the primary site of the tumor and enter the peripheral circulation, they are called circulating tumor cells (CTCs), capable of depositing in the lymph nodes and other organs, where they can proliferate and originate metastatic tumors. In this context, the present study includes both an experimental approach and a systematic literature review. The experimental approach aimed to quantify and characterize the CSC in fresh tumor tissue from primary OSCC lesions, associating biological properties related to the stem tumor and TEM phenotypes with the invasive and metastatic behavior of the OSCC. For this purpose, the expression levels of CD44 and ESA were evaluated by flow cytometry in fresh tissue samples in order to identify the CSC subpopulation as well as its CD44+ESA- (TEM/mesenchymal) and CD44+ESA+ (epithelial) subfractions, correlating these data to clinicopathological parameters. The results showed that the CD44+ESA- (mesenchymal) subpopulation was significantly associated with the degree of tumor differentiation and alcohol consumption, while the CD44+ESA+ (epithelial) subpopulation was directly correlated with the perineural invasion and regional lymph node compromising. Complementarily, considering the relevance of CTCs as minimally invasive biomarkers of cancer progression, as well as their phenotypic plasticity, a systematic review of CTC detection methodologies specifically in OSCC was performed.