Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression
Technical Report,24 Sep 2014,23 Sep 2015
Easter Virginia Medical School Norfolk United States
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Prostate cancer remains the most prevalent form of non-skin cancer in males and the second leading cause of cancer deaths in men within the U.S. MicroRNAs MiRNAs constitute an important class of non-coding RNAs that function as tumor suppressor genes, oncogenes, and metastatic factors in human prostate cancer and hold promise as novel therapeutic tools for prostate cancer. New evidence reveals miRNA activity is not confined to the cells in which they are produced, but can also signal intercellularly to other cells and tissues at distant sites via exosomal transport. We hypothesize that miRNAs specifically packaged in these 40-100 nm microvesicles and secreted from prostate cancer cells are important in the progression to aggressive disease. In this exploratory award, we are investigating the functional significance of exosomal miRNAs in prostate cancer. We are characterizing the miRNA composition within the cellular versus exosomal fractions of various syngeneic human prostate cancer cell lines that differ in their metastatic status in order to identify tumor suppressive exosomal miRNAs. We will subsequently test if exosomal delivery of tumor suppressor miRNAs modulates the behavior of aggressive human prostate cancer cell lines in vitro as well as in vivo using mouse xenograft models.