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Abstract Media supplemented with sera from acutely exercised men has been shown to have ‘anti‐cancer’ effects on prostate and breast cancer cell lines. This study investigated whether media supplemented with plasma samples taken at rest (≥30 h since the most recent exercise session) from men who were endurance‐trained (END), strength‐trained (STR) or recreationally active controls (CON) impacted the results of four assays that mimic hallmarks of cancer (proliferation, migration, extracellular matrix invasion and anoikis resistance) in the BT‐549 breast cancer cell line. Compared to control conditions of either serum‐free media or fetal bovine serum as appropriate, BT‐549 cells cultured with plasma‐supplemented media regardless of group resulted in greater cell proliferation (∼20–50%) and cell migration (∼15–20%), and lower extracellular matrix invasion (∼10–20%) and anoikis resistance (∼15–20%). Supplementing media with plasma from END or STR did not impact any outcomes of these assays compared to plasma from CON. Media supplemented with human plasma can impact functional assays reflective of cancer hallmarks in BT‐549 cells, but effects of exercise on proliferation, migration, extracellular matrix invasion and anoikis resistance were not evident in resting blood samples of individuals with a prior history of exercise training.

Blood–brain barrier (BBB) dysfunction is a key hallmark in the pathology of many neuroinflammatory disorders. Extracellular vesicles (EVs) are lipid membrane-enclosed carriers of molecular cargo that are involved in cell-to-cell communication. Circulating endothelial EVs are increased in the plasma of patients with neurological disorders, and immune cell-derived EVs are known to modulate cerebrovascular functions. However, little is known about whether brain endothelial cell (BEC)-derived EVs themselves contribute to BBB dysfunction. Human cerebral microvascular cells (hCMEC/D3) were treated with TNFα and IFNy, and the EVs were isolated and characterised. The effect of EVs on BBB transendothelial resistance (TEER) and leukocyte adhesion in hCMEC/D3 cells was measured by electric substrate cell-substrate impedance sensing and the flow-based T-cell adhesion assay. EV-induced molecular changes in recipient hCMEC/D3 cells were analysed by RT-qPCR and Western blotting. A stimulation of naïve hCMEC/D3 cells with small EVs (sEVs) reduced the TEER and increased the shear-resistant T-cell adhesion. The levels of microRNA-155, VCAM1 and ICAM1 were increased in sEV-treated hCMEC/D3 cells. Blocking the expression of VCAM1, but not of ICAM1, prevented sEV-mediated T-cell adhesion to brain endothelia. These results suggest that sEVs derived from inflamed BECs promote cerebrovascular dysfunction. These findings may provide new insights into the mechanisms involving neuroinflammatory disorders.