Abstract

Stressing Out the Neighbors: Stressed Exosomes (“SexOsomes”?) Passage Stress Phenotypes to Recipient Cells

Michael Graner, Professor, University of Colorado Anschutz School of Medicine

Cancer cells undergo numerous stresses, many of them self-inflicted, but often do not appear to suffer the consequences of those stresses. In some cases, the stress responses are actually beneficial to the tumor cells, providing them with potent resilience to their less-than-hospitable environments. One consistent tumor stress is the Unfolded Protein Response (UPR), an endoplasmic reticulum-based stress-management system with sensors, transducers, and effectors that result in a transcriptional/translational landscape rearrangement leading to resolution of the stress, or cellular apoptosis. However, tumors may incorporate the UPR into their stress portfolio to survive or even thrive amidst their environmental insults. We propose that exosomes from stressed cells (stressed exosomes, or “sexosomes”) are able to induce stress response phenotypes in recipient, unstressed cells, thus enabling stress responses without having to experience the actual stress. Our analysis in this report goes to the molecular level, monitoring proteome changes in glioma cells when those cells are exposed to exosomes released from UPR-stressed cells. We find high overlap in the proteomes of stressed cells and unstressed cells that receive “sexosomes”, suggesting that tumors may unify their overall stress responses despite their inherent heterogeneity. The implications for general tumor biology, and in particular, therapeutic resistance, are highlighted.