Background
The leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is considered a cancer stem cell marker, and is often overexpressed in tumors. The interaction between Lgr5 and the immune-related tumor microenvironment is not completely understood. The
Conclusion
Tregs promoted increased Lgr5 expression in GC cells via TGF-β1 and TGF-β1 signaling pathway, which may involve activation of the Wnt signaling pathway. High Lgr5 expression via TGF-β confer poor prognosis in gastric cancer.
Methods
Lgr5 expression was examined in 180 GC tumors by immunohistochemistry, and in 80 pairs of GC tumors for analysis of Th1/Th2 cytokines by ELISA. In addition, SGC7901 cells were co-cultured with patient-derived Tregs, varying concentrations of TGF-β1, TGF-β1 neutralizing antibody, or TGF-β receptor inhibitor SB431542, and Lgr5 and β-catenin expression were examined by qRT-PCR and western blot.
Results
In this study, an immunosuppressive microenvironment was associated with high Lgr5 expression in GC. Furthermore, Lgr5 expression was up-regulated in GC cells co-cultured with Tregs or treated with exogenous TGF-β1. This up-regulation was partially inhibited by the TGF-β1 neutralizing antibody, or TGF-β1 receptor antagonist SB431542. β-catenin was up-regulated with high Lgr5 expression induced by exogenous TGF-β1, and this up-regulation was inhibited by SB431542. An increased number of Tregs and high Lgr5 expression in GC tissues were significantly associated with low overall survival.