Co-culturing with PDSS2-Del2 overexpressed HCC cells stimulates the PI3K/AKT signaling pathway in macrophages, promotes macrophage differentiation towards the M2 type, and induces MMP2/MMP9 secretion, thereby providing a suitable microenvironment for tumor metastasis (Fig. 6E). This evidence concerns the gene MMP9 and hepatocellular carcinoma.