Abstract 5340: Retrovirus insertion induces syncytin mediated exosomes delivery in prostate cancer cells

Abstract

Abstract Activation of retroviruses in normal cells can induce tumors and a wide array of cancers contains retrovirus-like particles. The potential role of these endogenous retroviruses in the development and progression of tumors has been discussed in many studies. However the effects of retrovirus insertion into cancer cells have not yet been fully examined. In this study, we explore genetic material transfer either between retrovirus-transduced prostate cancer PC3 cells or between PC3 cells and their host environment through extracellular vesicles (EV) and virus-like particles. For these purposes, we transduced PC3 cells with either GFP-encoding retrovirus or with m-cherry-encoding lentivirus. Co-incubation of GFP-expressing cells with m-cherry-expressing cells for 72h yielded yellow PC3 cells. Yellow cells were also observed in the experiments where lentiviral m-cherry expressing PC3 cells were cultured with tissue culture medium from retrovirus GFP expressing PC3 cells. These results indicated that horizontal genetic information transfer involves neither fusion nor contact between the cells. Since incubation of the retrovirus GFP-expressing PC3 cells with the medium from the lentivirus m-cherry expressing PC3 cells, did not yield yellow cells the genetic material transfer requires retrovirus insertion in PC3 cells. Using Western blot and Q-PCR, we found the exosomes from the medium generated by retrovirus GFP expressing PC3 cells to carry human endogenous retroviral proteins syncytin 1 and 2 and contain RNAs encoding these proteins. Exosomes from the lentivirus m-cherry expressing PC3 cells had lower protein expression of Syncytin 1&2 than exosomes from retrovirus GFP expressing PC3 cells. Application of Syncytin 1 or 2 antibodies to the medium generated by or co-cultured retrovirus GFP expressing PC3 and lentivirus m-cherry expressing PC3 cells suppressed horizontal transfer of the genetic information from retrovirus GFP expressing PC3 cells to other cells. The specific mechanisms by which retroviral transduction and syncytins control the generation of a GFP-encoding pseudotyped retrovirus or EV and the delivery of their content, as well as the role of the virus/EV-mediated horizontal genetic material transfer between prostate cancer cells and between prostate cancer and their microenvironment remain to be clarified. Citation Format: Berna Uygur, Leonid Chernomordik. Retrovirus insertion induces syncytin mediated exosomes delivery in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5340. doi:10.1158/1538-7445.AM2017-5340