Mesd is a general inhibitor of different Wnt ligands in Wnt/LRP signaling and inhibits PC‐3 tumor growth in vivo

Mesd is a specialized chaperone for Wnt co‐receptor low‐density lipoprotein receptor‐related protein‐5 (LRP5) and LRP6, which contain four β‐propeller/epidermal growth factor modules, named E1 to E4 from N‐ to C‐terminal, in their extracellular domains. Herein, we demonstrated that recombinant Mesd protein is a general Wnt inhibitor that blocks Wnt/β‐catenin signaling induced not only by LRP6 E1‐E2‐binding Wnts but also by LRP6 E3‐E4‐binding Wnts. We also found that Mesd suppressed Wnt/β‐catenin signaling induced by Wnt1 in prostate cancer PC‐3 cells, and inhibited tumor growth in PC‐3 xenograft model. Our results indicate that Mesd is a universal inhibitor of Wnt/LRP signaling on the cell surface.