Irradiation of prostate cancer alters circulating small extracellular vesicle functions.

It is known that β1 integrins and a downstream signaling molecule c-Src are upregulated in prostate cancer (PrCa) tissues, are co-expressed in circulating small extracellular vesicles (sEVs) and contribute to cancer progression. Here, we demonstrate that sEVs from PrCa patients show robust expression of both β1 integrins and c-Src. The impact of irradiation, a widely used therapy for the treatment of PrCa, on circulating sEVs is however not fully understood. We show that sEVs isolated from the plasma of transgenic adenocarcinoma of mouse prostate (TRAMP) mice, stimulate migration and anchorage-independent growth of recipient cancer cells, but sEVs are not active when isolated from mice that had undergone pelvic irradiation of PrCa. In addition, circulating sEVs from irradiated mice do not show co-sedimentation of β1 integrins and either c-Src or sEV markers, previously observed in sEVs from non-irradiated mice, but show reduced expression of c-Src. To rule out that the observed effect of irradiation on sEVs is not due to reduced tumor size, we demonstrate that irradiation of PrCa cells in vitro diminishes sEV capability to stimulate recipient cell anchorage-independent growth. Irradiation-induced changes in the composition of circulating sEVs illustrate a tumor-suppressive effect of radiation, which may have potential therapeutic implications.