ObjectiveTo explore the effect of exosomal-miRNAs from tumor necrosis factor-like weak inducer of apoptosis(TWEAK)-stimulated macrophages(TMs) on the metastasis of bladder cancer cells.

MethodsThe characteristics of exosomes derived from TWEAK-stimulated TMs, THP-1 induced differentiation were observed.Through the miRNAs microarray analysis, the expressions of miRNAs in exosomes derived from TMs treated with or without TWEAK were detected.The internalization of bladder cancer ATCC5637 cells and miRNAs after the internalization were detected by the laser scanning confocal microscope.The effect of exosome from TWEAK-stimulated TMs on metastasis and signal-pathway in ATCC5637 cells were detected.

ResultsTWEAK not only increased the levels of miR-17-3p in TMs and the secreted exosomes, but also resulted in an elevated levels of miR-17-3p in recipient ATCC 5637 cells, which eventually reduced the activity of the EGFR/AKT/ERK 1/2 pathway.Pre-transfection of antagomiR-17-3p in TMs substantially decreased the levels of miR-17-3p in macrophages, its secreted exosomes and the recipient ATCC 5637 cells with a concomitant enhancement of ATCC 5637metastasis, suggesting an involvement of exosomal miR-17-3p from TMs in modulating the metastasis of ATCC 5637cells.And miR-17-3p inhibited the metastasis of bladder cancer cells via the EGFR/AKT/ERK 1/2 pathway.

ConclusionsTWEAK transfers exosomal miRNAs to bladder cancer cells via TMs to inhibit the EGFR/AKT/ERK 1/2 pathway, resulting in the inhibition of metastasis in bladder cancer cells.