Neoplastic exosomes in human head and neck cancers promote angiogenesis and tumor progression in vitro and in vivo as a result of reprogramming the cancer microenvironment

Head and neck squamous cell cancer (HNSCC) is a group of cancers that affect the mouth, pharynx, larynx, nose and paranasal sinuses. They represent over 90% of all malignant neoplasms in this region. In 2012, over 600,000 new cases of HNSCC were registered worldwide, making these cancers the seventh most common human cancer. Despite multicentre research on HNSCC, as well as the development of new therapeutic concepts and diagnostic methods, the average 5-year survival has remained below 50% for 4 decades. Thus, there is an urgent need to identify novel biomarkers and therapeutic approaches for HNSCC. Adequate vascularization is essential for the growth of solid tumors such as HNSCC. Tumor angiogenesis is based on the mechanisms of classical angiogenesis. Tumors are able to increase their own vascularity by producing angiogenic factors or use tumor cells to migrate close to existing vascular structures and mimic endothelial cells (ECs) or differentiate into ECs. Recent years of research into the effects of cancer on its own microenvironment and the host's immune system focuses on micro-vesicles (EVs), which are spherical structures 30-150 nm in diameter, also known as 'exosomes.' EVs are produced by all types of cells but tumor cells are particularly active producers of tumor-derived exosomes (TEX). Exosomes contain a whole panel of different particles such as DNA, mRNA and microRNA (miR), enzymes, growth factors, etc. Research in recent years has shown that TEX play an important role in suppressing the immune system in the tumor microenvironment (TME) which promotes tumor progression. Moreover, the influence of TEX on the development of blood vessels and angiogenesis is also suspected. Therefore, based on our preliminary research results and literature data, we hypothesize that TEX influence the proliferation of ECs and angiogenesis in the HNSCC microenvironment. Therefore, the aim of the present project is to investigate the role of TEX in the angiogenesis and progression of HNSCC and to investigate the mechanisms underlying this process using in vitro, in vivo and ex vivo models.