Extracellular fibronectin influences on OSCC migration, invasion and macrophage phenotype

• Grant number: 22/01681-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2022
• End date: April 30, 2023
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Carlos Rossa Junior
• Grantee: Mayara Cristina Zunareli
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 20/00394-2 - Head and neck squamous cell carcinoma (HNSCC) invasion and distant metastasis: relevance and crosstalk between GALR2 and efferocytosis in the tumor microenvironment and hematogenic dissemination, AP.TEM

Abstract

Neoplastic cells gain the migratory and invasive phenotype by going through the epithelial-mesenchymal transition (EMT), which involves changes in cell-cell (via cadherins) and cell-matrix (via integrins) contacts. Fibronectin is a major constituent of the extracellular matrix of oral cavity squamous cell carcinoma (OSCC), and its expression level/relative amount is associated with a worse prognosis. Fibronectin influences various cellular activities, such as adhesion, migration, growth, and differentiation, and can increase tumor invasion and metastasis. Macrophages are antigen-presenting cells and are present in large numbers within solid tumors (TAMs, tumor-associated macrophages), where they may represent up to 50% of the tumor mass. The amount of TAMs in OSCC is inversely related to prognosis. Thus, the hypothesis of this study is that the presence of fibronectin influences the phenotype of tumor cells and macrophages, as well as the migration and invasion of neoplastic cells in co-culture with macrophages. The specific objectives are: (I) evaluate the effect of fibronectin on the phenotypic profile of macrophages and OSCC tumor cells: the macrophage phenotype will be evaluated by the expression of CD11b, CD14, CD163, CD80 by flow cytometry, and the epithelial-mesenchyme transition phenotype of tumor cells by the expression of EpCAM by flow cytometry; and (II) evaluate the effect of fibronectin on OSCC migration and invasion in co-culture with macrophages: migration will be evaluated by the in vitro wound healing experiment and invasion in myogel. (AU)