Ligand-receptor pairs with a preference for stroma-to-tumor signaling include BMP10-ACVR2B, FGF16-FGFR4, FGF5-FGFR4, INSL3-RXFP2, RLN3-RXFP2, RSPO1-LRP6, RSPO3-LGR4, and RSPO3-LRP6 (Figure 2). Here, LRP6 is linked to neoplasm.