Cancer Associated Fibroblasts Regulate The Proliferation Of Prostate Cancer Cell Line PC-3 By TGF-?R?/Smad7

Objective To explore the impact of cancer-associated fibroblasts(CAFs)on the growth of prostate cancer cell PC3?LNCaP by TGF-beta R ?/smads signaling pathway and the role of key protein TGF-PRII,Smad2 and Smad7 underling it.Methods CAFs from human prostate cancer tissue was primary cultured,and then treated with TGF-beta receptor type II(TGF-beta RII)antagonist(LY2109761).The conventionally cultured CAFs were used for control.The prepared condition mediums were designated as CAFs-LY-CM,and CAFs-CM respectively.The expression of TGF-beta receptor II in CAFs,PC3 and LNCaP cells was detected by Western blotting.The difference on proliferation capacity and levels of Phosphorylated Smad2(P-Smad2).Smad7 of PC3 and LNCaP cells in this two conditional mediums were investigated.Results CAFs and PC3 cells were positive for TGF-beta R ?,while LNCaP cells were weakly positive.0.75g/L CAFs can significantly promote the proliferation of both PC3 and LNCaP cells.CAFs-CM could up-regulate the expression of Smad7 protein in PC3 cells(6.36±0.65 vs 2.94±0.19,P<0.05),but had no effect on the expression of P-Smad2 protein in LNCaP cells(5.06 ± 0.38vs2.86 ± 0.39,P<0.05).After 10-6mol/L LY2109761 treatment,CAFs-LY-CM could significantly inhibit the proliferation of PC3(4.09±0.36 vs 6.36±0.65,P<0.05),which was dose dependent,but not significantly inhibited the proliferation of LNCaP cells.Conclusions CAFs is a potential therapeutic target for PCa through the regulation of PC3 proliferation by TGF-PRII/Smad7.CAFs regulates the proliferation of LNCaP cells by TGF-?/Smads signaling pathway have no significant,there are other molecular mechanisms.