Blocking IGF-1/ERβ/Bcl-2 signalling by either an shRNA targeting ERβ or an anti-IGF-1 neutralizing antibody partially reversed the capacity of CAFs to increase BCa chemoresistance.
Together, these results might aid in the development of new therapies via targeting of this ERβ-mediated signal pathway to better suppress BCa progression.
Mechanism dissection revealed that the enhanced BCa cell invasion could function via up-regulation of the estrogen receptor beta (ERβ) in both mast cells and BCa cells, which resulted in the increased CCL2/CCR2/EMT/MMP9 signals.
Supportively, treating cells with the ERβ-specific antagonist, 4-[2-Phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP), reduced BCa cell growth and invasion, as well as MCM5 expression.
Identification of estrogen receptor-β (ERβ) in up to 75 % of urinary tumors raises the question of whether this receptor could be targeted to effectively treat bladder cancer.