TMPRSS2-ERG Fusion Promotes Recruitment of Regulatory T cells and Tumor Growth in Prostate Cancer.

BACKGROUND

This study was designed to examine the effect of transmembrane protease serine 2 ETS-related gene (TMPRSS2-ERG) fusion on regulatory T cells and tumor growth in prostate cancer, which may provide a new potential therapeutic direction for PCa.

METHODS

The effect of TMPRSS2-ERG fusion on the migration of Treg cells and tumor growth in a mouse model was investigated in vitro and in vivo. TMPRSS2-ERG fusion in biopsy tissues was performed by fluorescence in situ hybridization and the expression of ERG and Forkhead box P3 was detected by gel electrophoresis, real-time quantitative reverse transcription polymerase chain reaction and Western blot. Enzyme-linked immunosorbent assay and flow cytometry were used to analyze transforming growth factor β levels and the number of regulatory T cells, respectively. Finally, the infiltration of regulatory T cells was analyzed by Forkhead box P3 immunohistochemistry.

RESULTS

Fluorescence in situ hybridization analysis showed that the TMPRSS2-ERG fusion gene was positive in prostate cancer and that the messenger RNA and protein expression of ERG were significantly up-regulated in prostate cancer biopsy tissues. Furthermore, the number of regulatory T cells and the levels of Forkhead box P3 and transforming growth factor β were significantly increased in prostate cancer. TMPRSS2-ERG fusion increased the migration and activation of regulatory T cells in vitro and promoted subcutaneous tumor size and regulatory T cells infiltration in mouse models.

CONCLUSIONS

TMPRSS2-ERG fusion can regulate the recruitment and infiltration of regulatory T cells to promote tumor growth in prostate cancer.