AWARD NUMBER: W81XWH-10-1-0544 TITLE: Biomarkers in the Detection of Prostate Cancer in African Americans PRINCIPAL INVESTIGATOR:

Exosomes are small bilayer-membrane-bound nanoparticles that are released from normal, diseased, and neoplastic cells and are present in blood and other bodily fluids. Exosomes contain a variety of signal molecules including signal peptides, mRNA, microRNA (miRNA), and lipids and have characteristic molecular features on their external surfaces (e.g., CD9 and CD81). Exosomes can function to export from cells unneeded endogenous molecules and therapeutic drugs. When exosomes and similar types of vesicles are secreted from cells and are taken up by other cells, they may act locally to provide autocrine or paracrine signals or distantly as a newly described nanoparticle-based endocrine system. Specifically, mRNA transferred to cells by exosomes can result in the production of new and novel proteins. In cancer, signals via exosomes affect the immune system via inhibition of the functions of T cells and natural killer (NK) cells, by inhibiting the differentiation of precursors to mature antigen-presenting cells, e.g., dendritic cells, and by increasing the number and/or activity of immune suppressor cells including myeloid-derived suppressor cells, T regulatory cells, and CD14, HLA-DR−/low cells. Exosomes from neoplastic lesions also act to provide a fertile environment in which neoplastic lesions can develop, progress, and metastasize, especially via the stimulation of angiogenesis. Exosomes have multiple potential clinical uses including the development of vaccines for targeting tumors; also, tumor-derived exosomes may be useful in diagnosis/early detection, risk assessment and prediction, in determining prognosis, and as surrogate endpoints in evaluating therapeutic and preventive approaches to cancer.