This is consistent with a previous study reporting that hepatocytes with upregulated SAA1 and SAA2 expression provided a pro-metastatic niche for liver metastasis in a mouse model of pancreatic cancer.28 Alternatively, complement components secreted by hepatocytes, including C3a and C5a, could recruit macrophages via C3AR1/C5AR1,53 and CSF1 secreted by tumor cells could promote macrophage M2 polarization via SIRPA/CSF1R54 in the invasive zone, indicating that the invasive zone is a sophisticated ecosystem with multi-directional interactions. Here, C3AR1 is linked to familial pancreatic carcinoma.