Exosomal RNA mediates transformation of nontumorigenic human bronchial lung epithelial cells

Exosomes are nanovesicles with a diameter between 30-150 nm. Exosomes are produced and released by all cell types into body fluids and, thus, play a major role in cell-cell communication through the transfer of proteins, lipids, and nucleic acids into recipient cells. Uptake of bioactive cargo into recipient cells can impart physiologic and biologic changes in the recipient cell. Especially in cancer, exosome released from cancer cells can reprogram cells, driving various hallmarks of cancer, such as proliferation, migration, invasion, and angiogenesis. In this study we evaluated the effects of exosomes, isolated from non-small cell lung cancer (NSCLC) cells, on nontumorigenic human bronchial epithelial cells (HBECs). Firstly, we determined that cancer cells generate more exosomes than nontumorigenic cells and that cancer cell-derived exosomes are readily taken up by nontumorigenic cells. The nontumorigenic cells exposed to NSCLC-derived exosomes gained the ability to migration and invade. In parallel, we observed that NSCLC-derived exosomes promoted changes in epithelial-to-mesenchymal gene profiles, supporting the conclusion that HBECs were becoming transformed. Exosomes were also capable of permeablizing a monolayer of human endothelial cells, suggesting that NSCLC-derived exosomes may disrupt the vasculature enhancing metastatic capabilities. Importantly, the transformative effects of the exosomes were mediated mostly by exosomal RNA. Comparing the RNA profile from a panel of cancerous exosomes to RNAs contained inside of exosomes isolated from nontumorigenic, one long noncoding RNA (lncRNA) was highly elevated. Knockout of this lncRNA greatly diminished the capability of the cancerous exosomes to promote the observed hallmarks of cancer, suggesting that a single lncRNA is responsible for the majority of the tumorigenic capacity of the exosomes. In vivo mouse modeling and patient-based evidence are currently under way to support these cell-based findings. Citation Format: Sarunya Kitdumrongthum, Sean Humphrey, Hana Kubo, Feng Tian, Sarah Allen, Nadia Atallah, Humna Hasan, Andrea L. Kasinski. Exosomal RNA mediates transformation of nontumorigenic human bronchial lung epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2477.