Study of the interactions between cells from the carcinoma of head and neck and its microenvironment

Abstract

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common type of cancer and most cases are diagnosed in advanced stages, limiting the chances of cure despite therapeutic options.There is ample evidence that the initiation and progression of cancer depend not only on genetic characteristics but also on various components of the tumor microenvironment, including inflammatory and immune cells (lymphocytes, macrophages and mast cells), fibroblasts, endothelial cells, adipocytes and extracellular matrix. This project aims to analyze the secretome of HNSCC cells in different conditions and to investigate its effect on the phenotype of the neoplastic cell and on tumor - microenvironment interactions. Its specific objectives include: (a) to develop computational tools to automate the process of searching for genes, proteins and metabolites with altered expression in HNSCC, as well as to select those which are relevant to head and neck tumorigenesis and tumor - microenvironment interactions; (b) to analyze the set of proteins and metabolites secreted by HNSCC cells subjected to hypoxic conditions, inhibition of autophagy and in the presence of compounds used for treatment of cancer; (c) to asses, in untreated neoplastic epithelial cells, changes in morphology, proliferation index, migration, invasion and composition of the secretome caused by paracrine factors synthesized by HNSCC cells under stress conditions; (d) to assess, in cells of the immune system and in normal fibroblasts, changes in morphology, proliferation rate and composition of secretome caused by paracrine factors synthesized by HNSCC cells in conditions of stress; (e) to assess the effect on the morphology, proliferation, migration and invasiveness of epithelial cancer cells caused by ectopic expression of the kalicreine, a differentially expressed serine protease in HNSCCs.The results may contribute to understand the effect of paracrine factors released by neoplastic cell on stromal and tumor cells. (AU)