As expected, due to the ligand–receptor feedback mechanism, when HCC cell lines, Huh7, PLC, and MHCC-LM3 were co-cultured with THP-1 CTRL or THP-1 shSPP1 in vitro, respectively, CD44 levels declined in THP-1 shSPP1 co-cultured cells (Supplementary Fig. S6a, b). Here, CD44 is linked to hepatocellular carcinoma.