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Investigation of amoeboid cells in Oral Squamous Cell Carcinoma and their participation on metastasis

Grant number: 17/25022-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2018
Effective date (End): January 31, 2022
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Camila de Oliveira Rodini Pegoraro
Grantee:Rafael Carneiro Ortiz
Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
Associated research grant:13/07245-9 - Investigation of the role of cancer stem cells and microenvironment on epithelial-to-mesenchymal transition, invasion and metastasis in oral squamous cell carcinoma, AP.JP

Abstract

Oral Squamous Cell Carcinoma (OSCC) is one of the most common cancer in the head and neck and results in high morbidity and mortality annually, being the worst prognosis related to the presence of metastasis in cervical lymph nodes. Metastasis has been associated with a subpopulation of tumor cells, called Cancer Stem Cells (CSCs), which consists of a small population with stem-like cells properties. 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 tumor. Currently, it is believed that CSCs capable of migrating and colonizing distant sites have the amoeboid phenotype and may or may not be in EMT. In this context, the purpose of this study is to quantify and characterize CSC in OSCC, both in paraffin-embedded primary tumor tissues and corresponding metastatic lymph nodes, as well as in peripheral blood samples from patients with advanced stage of the disease, aiming to evaluate the association of the biological properties related to stem-like phenotype and amoeboid, with the invasive and metastatic behavior of OSCC. To achieve this goal, the expression of amoeboid markers will be detected by immunofluorescence in paraffin-embedded tumor tissue samples in order to identify the subpopulations of CSC on amoeboid phenotype, and results will be subsequently related to clinic-pathological parameters. Peripheral blood CTCs from patients with advanced OSCC will be isolated, quantified and characterized by immunofluorescence and qPCR, in relation to their CSC and amoeboid (CTCs) phenotypes. It is believed that at the end of the project the study of CSC may be able to provide prognostic valuable information, as well as the identification of amoeboid CSC in primary tumors, peripheral blood and metastatic lymph nodes can be used in the future as risk predictor of metastasis and therapeutic efficacy in OSCC control. (AU)