Estrogen Receptor Alpha (ERα)-Associated Fibroblasts Promote Cell Growth in Prostate Cancer

Estrogen receptor (ER) is expressed in cancer-associated fibroblasts (CAFs) in the stromal compartment of cancerous prostate. However, the effect of ER alpha in CAF cells on prostate cancer (PCa) cell growth remains unclear. We used lentiviral transduction to stably express ER alpha in CAF cells isolated from transgenic adenocarcinoma of the mouse prostate model. MTT and 3D colony-formation assays demonstrated that conditioned medium from ER alpha-expressing CAF cells (CAF-ER alpha+) promoted cell proliferation and colony growth of various PCa cell lines, such as PC3, LNCaP, 22RV1, and C4-2. We further confirmed the in vitro data by orthotopically co-implanting 22RV1, transfected with firefly luciferase, and CAF-ER alpha+ cells in vivo using mouse model. Mice co-implanted with CAF-ER alpha+ exhibited stronger luciferase signals and bigger tumor size compared to animals co-implanted with CAF that do not express ER. Our results demonstrate that ER expressed in CAF might play a pro-proliferative role in PCa.