Abstract 779: The role of exosome-mediated cell-cell communication in inducing phenotypic changes

Abstract

Abstract A new class of intercellular communication has recently emerged that involves transfer of exosomes, especially during the interactions between tumor and the immune system. However, the advantage of exosome-mediated cell-cell communication over direct cell to cell communication mechanisms or through soluble factors is unclear. We have performed mass spectrometry based proteomic profiling of exosomes isolated from pancreatic cancer cell lines, for the exosome cell surface and for the protein cargo. The resulting profiles were compared with proteomic profiles of corresponding cell lysates. We uncovered substantial enrichment in protein pairs in exosomes across cell lines but not in cell lysates, suggestive of a mechanism of exosome-based protein sorting and packaging that favor specific protein combinations. Stochastic simulations and analytical analysis provide supportive evidence that exosomes enable recipient cells to rewire gene regulatory networks to induce robust phenotypic transitions among different gene states. Moreover, from the simulation of two-way exosome-mediated communication of two cell types, we show that cells could achieve synchronized decision making through exosomes. Our integrative approach provides new insights into unique features of exosome-mediated cell-cell communication. Citation Format: Mingyang Lu, Michela Capello, Satyendra C. Tripathi, Herbert Levine, Eshel Ben-Jacob, Samir M. Hanash, José Onuchic. The role of exosome-mediated cell-cell communication in inducing phenotypic changes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 779.