How Extracellular Vesicles in the Human Tumor Microenvironment Regulate Cancer Progression

Extracellular vesicles (EVs) have been shown to convey complex messages between cells by shuttling proteins and RNA from one cell to another. I have recently developed a state-of-the-art method to isolate distinct EV subpopulations from human tissues. In this project I will use that method to elucidate the mechanisms of EV communication within human tumor tissues.

Specifically, I will determine how EVs can influence the phenotype and function of the recipient cells in the tumor microenvironment.As the first step, I will analyze the cellular source of tumor tissue-derived EVs, and I will then isolate the tumor cellular components and treat them with EVs isolated from the same tumor tissue.

The EV uptake will be investigated by scanning confocal microscopy and transmission electron microscopy. e functional effects of EVs on recipient cells will be investigated by proteomic analysis and single cell RNA sequencing.

Moreover, I will describe which EV subpopulations, and specifically which EV components, are responsible for the functional effects in the recipient tumor cells.The results of this research will teach us how EVs mediate messages between cells in the tumor microenvironment, and this will likely contribute to the identification of EV-based biomarkers and will lay the foundation for novel uses of EVs for therapeutic purposes in patients with cancer.