Aquaporin 5 transfer via MDA-MB-231 cell extracellular vesicles increases recipient endothelial cell invasion.

Aquaporin 5 (AQP5), a water channel protein, is a known promoter of cancer metastasis, primarily through its role in enhancing cancer cell motility and invasion. While this function has been studied extensively in cancer cells themselves, the contribution of AQP5 to the behavior of other cells in the tumor microenvironment, particularly endothelial cells, remains less understood. Prior studies have linked secreted signals from cancer cells with higher AQP5 expression to increased endothelial angiogenic capacity, a key driver of metastasis. Separately, metastasis-associated proteins have been shown to transfer from cancer to endothelial cells via extracellular vesicles (EVs), promoting angiogenesis. In this study, we investigated whether AQP5-containing EVs influence endothelial cell behavior. We found that EVs derived from cancer cells with high AQP5 expression significantly enhanced the invasive capacity of recipient endothelial cells, a process essential to angiogenesis. These findings provide the first evidence that transfer of the prometastatic protein AQP5 via EVs can modulate endothelial cell function, highlighting a novel mechanism by which cancer cells manipulate their microenvironment to support metastasis.