Extracellular Vesicle Hallmarks of Viral Malignancies

Division Of Basic Sciences - Nci

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Abstract

The technological foundations and EV analytical strategies detailed in projects ZIA BC 011502, ZIA BC 011942, and ZIA BC 012107 have enabled our lab to begin to collaboratively investigate the unique pathogenic mechanisms and distinctive EV cargo signatures of viral associated malignancies. We are systematically characterizing EV cargo signatures from two distinctive virus-associated lymphoid malignancies: EBV-transformed lymphoblastoid cells (DNA virus-mediated) and HTLV-associated leukemia/lymphoma cells (retrovirus-mediated). By exploring the DNA, RNA, and protein cargo profiles of EVs from EBV- and HTLV-associated lymphomas, we have identified a short list of candidate cargo elements that are remarkably highly-conserved and which indicate that a novel viral:host interaction may be driving malignant transformations and lymphoma progression in ways not previously considered. By leveraging the same multiparametric, multi-omics methods that we developed and streamlined for solid tumor EVs related to metastatic potential (ZIA BC 011503), we are generating highly complementary datasets and have streamlined our inter-project pipeline refinement. Use of the same analytical workflows to study EV cargo from virus-associated malignancies as we are using to study solid tumor EV cargo associated with metastatic progression, is setting the groundwork for future analyses to fundamentally conserved mechanisms of tumor progression across different cancer etiologies. Through this integrated strategy, we are also testing how broadly applicable analytical methods may be for understanding other ways in which cancer EVs reflect or promote aggressive tumor traits, and for developing new classes of targeted therapies for virus-driven cancers.