Extracellular Vesicles Released from Cancer Cells Promote Tumorigenesis by Inducing Epithelial to Mesenchymal Transition via ß-Catenin Signaling.

ABSTRACT

Lung cancer is the leading cause of cancer-related deaths globally, in part due to a lack of early diagnostic tools and effective pharmacological interventions. Extracellular vesicles (EVs) are lipid-based membrane-bound particles released from all living cells in both physiological and pathological states. To understand the effects of lung-cancer-derived EVs on healthy cells, we isolated and characterized EVs derived from A549 lung adenocarcinoma cells and transferred them to healthy human bronchial epithelial cells (16HBe14o). We found that A549-derived EVs carry oncogenic proteins involved in the pathway of epithelial to mesenchymal transition (EMT) that are regulated by ß-catenin. The exposure of 16HBe14o cells to A549-derived EVs resulted in a significant increase in cell proliferation, migration, and invasion via upregulating EMT markers such as E-Cadherin, Snail, and Vimentin and cell adhesion molecules such as CEACAM-5, ICAM-1, and VCAM-1, with concomitant downregulation of EpCAM. Our study suggests a role for cancer-cell-derived EVs to induce tumorigenesis in adjacent healthy cells by promoting EMT via ß-catenin signaling.