Infiltrating neutrophils increase bladder cancer cell invasion via modulation of androgen receptor (AR)/MMP13 signals

Early studies indicated that several inflammatory immune cells, including macrophages, mast cells, B and T cells in the tumor microenvironment, might influence cancer progression. Here we found that bladder cancer (BCa) cells could recruit more neutrophils than normal bladder cells. The consequences of recruiting more neutrophils might then increase BCa cell invasion via up-regulating androgen receptor (AR) signals. Mechanism dissection revealed infiltrating neutrophils could up-regulate AR signals via either increased AR mRNA/protein expression or increased AR transactivation. The increased AR signals might then enhance BCa cell invasion via increasing MMP13 expression. Together, these results might provide us a new potential therapeutic approach to better battle BCa metastasis via targeting the newly identified signaling from infiltrating neutrophils to BCa through AR to MMP13 signals.