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Do Prostate Cancer Exosomes Generate a Field Effect Leading to Tumor Multifocality

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Chapman University Orange United States

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Prostate field effect or field cancerization denotes the presence of molecular aberrations featured in structurally intact cells of histologically normal tissues adjacent to adenocarcinomas, in many cases as distant as centimeters from the tumor margin. The presence of a field effect is causatively associated with the occurrence of tumor multifocality in the prostate, but a notable gap of knowledge is the lack of understanding of how multifocal fields of molecular aberrations in histologically normal tissues adjacent to tumors form. In this project, we have proposed a novel line of investigation that hypothesizes the implication pf tumor-derived exosomes in the formation of field effect and tumor multifocality. Exosomes are extracellular microvesicles secreted by cells for the purpose of inter-cell and inter-tissue communication. Their biological function lends itself for a potential involvement in the formation of pre-malignant fields, especially when they are secreted by pre-existing cancer cells into neighboring tissues with histologically normal architecture. We pursued two Specific Aims to test our hypothesis i To test the cellular and molecular effect of prostate cancer exosomes on non-cancerous cells, and ii to determine the association between markers of field effect and markers of exosomes in tissues adjacent to adenocarcinomas. Support from the DOD for this project has allowed us to i Establish the isolation and biochemical characterization of exosomes from prostate cells cancer ii determine the effects of tumor-derived exosomes on normal prostate epithelial cells iii determine the correlation between a marker of exosomes CD9 and at least one marker of field effect EGR-1 iv complete a manuscript and publish it, as well as prepare a second manuscript which is close to submission and v build strategically meaningful alliances with researchers at neighboring institutions.

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Technical Report,25 Mar 2015,24 Mar 2018



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Approved For Public Release;

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