Extracellular vesicles derived from oxidatively stressed stromal cells promote cancer progression

Abstract

Like many diseases, cancer is influenced by oxidative stress. Increases in oxidative stress caused by factors such as environmental stressors and unhealthy diets can increase the risk of cancer and worsen cancer prognoses. However, oxidative stress does not always promote cancer. On the contrary, many chemotherapeutics induce the production of oxidative stress to kill cancer cells. The tumor microenvironment (TME) is another factor in cancer progression. Stromal cells, a part of the TME, communicate with cancer cells through extracellular vesicles (EVs) - the primary vehicles for the delivery of messengers, including proteins, metabolites, DNA, and RNA. We hypothesized that the TME mediates cancer’s response to oxidative stress by delivering EVs to cancer cells. In order to test this hypothesis, we treated breast cancer cells (HCC1806, SKBR3, MCF7, and MDA-MB-436) and lung cancer cells (A549 and PC9) with EVs derived from oxidatively stressed stromal cells and compared their expression of marker proteins of cell proliferation and epithelial to mesenchymal transition to cancer cells treated with EVs from control stromal cells and untreated cancer cells. We found that EVs extracted from oxidatively stressed adipocytes increased the cell proliferation of breast cancer cells. Additionally, we found that EVs extracted from lung fibroblasts promoted epithelialmesenchymal transition in lung cancer cells. These findings present a novel way that the TME influences cancer progression. The findings of this paper can inform future cancer prevention studies.